Hodgkin DiseasePhase 1/2NCT02979522
A Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Participants With Advanced Stage Newly Diagnosed Hodgkin Lymphoma
A Phase 1/2 study testing Brentuximab vedotin, Doxorubicin and Vinblastine in people with Hodgkin Disease, run by Takeda at 14 sites in 4 countries.
Trial summary
The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as confirm the recommended dose of brentuximab vedotin (ADCETRIS) in combination with a multiagent chemotherapy regimen, doxorubicin (Adriamycin), vinblastine, and dacarbazine, in pediatric participants with advanced… Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Hodgkin Disease
- What is being tested?
- Brentuximab vedotin, Doxorubicin and Vinblastine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 14 sitesin 4 countries
- Study dates
- 6 Sep 2017to 24 Sep 2029
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Each participant must meet all the following inclusion criteria to be enrolled in the study:
- Histologically confirmed CD30+ classical HL.
- Advanced stage, newly diagnosed HL (Stage III and Stage IV disease).
- Treatment-naive HL.
- Have performance scores of greater than or equal to (>=) 50 for Lansky Play-performance or Karnofsky Performance Status.
- Have bidimensional measurable disease as documented by radiographic technique per International Working Group (IWG) criteria.
- Have adequate blood counts, renal and liver function as defined in the protocol.
Who cannot join
- Nodular lymphocyte predominant HL.
- Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML.
- Any sensory or motor peripheral neuropathy.
- Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.
- Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks before the first study protocol therapy.
- Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of AVD.
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- Known human immunodeficiency virus positive.
- Known hepatitis B surface antigen positive or known or suspected active hepatitis C infection, as determined by hepatitis B DNA or hepatitis C RNA, respectively, in blood.
- Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Use of any strong or listed moderate cytochrome P450 (CYP) 3A4 inhibitors less than (<) 2 weeks before the first dose of protocol therapy (please refer to the Study Manual for an example list of prohibited CYP3A4 inhibitors).
- Any of the following cardiovascular conditions or values within 6 months before the first dose of protocol therapy:
- Shortening fraction of <27 percent (%) by echocardiogram or, if echocardiogram not feasible, ejection fraction of <50% by radionuclide angiogram (RNA or MUGA [multiple-gated acquisition scan]).
- New York Heart Association Class III or IV heart failure.
- Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
Trial locations and contacts
14 sites in 4 countries.
14 sites in 4 countries
Brazil6 sites
Jardim das Americas
Paranã, 81520-060
INCA - Instituto Nacional de Cancer
Rio de Janeiro, 20230-230
Hospital Sao Rafael S/A
Salvador, Estado de Bahia, 41253-190
GRAACC - Grupo de Apoio ao Adolescente e a Crianca com Cancer
São Paulo, 04023-062
ICr - Instituto da Crianca - HCFMUSP
São Paulo, 05403-000
Hospital Santa Marcelina
São Paulo, 08270-070
Italy4 sites
Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
Florence, 50139
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Ospedale Pediatrico Bambino Gesu,UOC Onco-ematologia
Roma, 165
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino, 10126
United States2 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Japan2 sites
St. Marianna University School of Medicine Hospital
Kawasaki-shi, Kanagawa, 216-8511
NHO Nagoya Medical Center
Nagoya, Aichi-ken, 460-0001
About this study
Official title: An Open-Label Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Patients With Advanced Stage Newly Diagnosed Hodgkin Lymphoma
The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as confirm the recommended dose of brentuximab vedotin (ADCETRIS) in combination with a multiagent chemotherapy regimen, doxorubicin (Adriamycin), vinblastine, and dacarbazine, in pediatric participants with advanced stage newly diagnosed classical CD30+ Hodgkin Lymphoma (HL).
Read the detailed description
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat pediatric participants who have advanced stage, newly diagnosed, classical CD30+ HL. This study will assess the safety, tolerability, and anti-tumor activity, as well as recommended dose of brentuximab vedotin in combination with a multiagent chemotherapy regimen that is based on a current standard of care (SOC) first-line treatment regimen for newly diagnosed HL.
The study will enroll approximately 55 evaluable participants. The study will be conducted in 2 phases, Phase 1 and Phase 2. Phase 1 study will enroll at least 6 participants to determine the recommended dose. Once the recommended dose is identified additional participants will be enrolled into phase 2 so that the total number of evaluable participants will be at least 55, including participants treated at recommended dose in Phase 1. Participants will be enrolled to the following initial dose cohort with an option to explore a reduced dose cohort at 36 mg/m^2 if needed:
- Brentuximab vedotin 48 mg/m^2 in combination with doxorubicin, vinblastine, and dacarbazine.
This multi-center trial will be conducted in the United States, Italy, Brazil and Japan. The overall time to participate in this study is approximately 55 months, including the follow-up period. Participants will be followed for a maximum of 30 days following the last dose of protocol therapy for a follow-up assessment and will be followed for survival and disease status every 12 weeks for 12 months, and then every 24 weeks until death or study closure or for up to 2 years from the date of the last participant enrolled.
- Conditions
- Hodgkin Disease
- Being tested
- Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine
- Keywords
- Drug therapy, pediatric Hodgkin disease, frontline Hodgkin disease, advanced stage Hodgkin disease, pediatric lymphoma
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brentuximab vedotinDrug
Also called Adcetris
Brentuximab vedotin infusion
DoxorubicinDrug
Also called Adriamycin
Doxorubicin infusion
VinblastineDrug
Vinblastine infusion
DacarbazineDrug
Dacarbazine infusion
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD | Experimental | Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. Receives: Drug: Brentuximab vedotin; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine |
| Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Experimental | Brentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. Receives: Drug: Brentuximab vedotin; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population
The recommended dose was determined after considering all safety data in phase 1 and assessing for dose limiting toxicities (DLTs) which are defined as the dose range at which less than or equal to (<=) 1 of 6 evaluable participants experience DLT within the defined observation period (Cycle 1 + 28 days). This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: From the first dose (Cycle 1) up to Day 56 (Cycle length=28 days)
Phase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Phase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, Is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, Is a congenital anomaly/birth defect, Is a medically important event.
Measured: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in the statistical analysis plan (SAP) , data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: At end of treatment (EOT) visit 30 days after the last dose of study drug (at Month 7)
Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: From first dose of study drug up to Cycle 2 Day 25 (Each Cycle length=28 days)
Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit
PR was defined as regression of measurable disease and no new sites as assessed by IRF as per IWG criteria. Percentage of participants in the response-evaluable population who achieved a partial response based on the IRF assessment at the EOT visit based on the IWG criteria are reported. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: At EOT visit 30 days after the last dose of study drug (at Month 7)
Phase 2: Percentage of Participants Who Achieved an Overall Response Rate (ORR) Per IRF Assessment Per IWG Criteria at EOT Visit
Overall response rate was defined as the percentage of participants with CR or PR as assessed by IRF using IWG criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new diseases. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: At EOT visit 30 days after the last dose of study drug (at Month 7)
Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose
This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)
Secondary outcomes (49)
Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb)
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE)
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Measured: At EOT visit 30 days after the last dose of study drug (at Month 7)
Phase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit
PR was defined as regression of measurable disease and no new diseases as per IWG Criteria based on IRF. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Measured: At EOT visit 30 days after the last dose of study drug (at Month 7)
Phase 1: Percentage of Participants Who Achieved an ORR Per IRF Assessment Per IWG Criteria at EOT Visit
Overall response rate was defined as the percentage of participants with CR or PR as assessed by an IRF using IWG Revised Response Criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new sites. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Measured: At EOT visit 30 days after the last dose of study drug (at Month 7)
Phase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Measured: From first dose of study drug up to Cycle 2 (Each Cycle length=28 days)
Phase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET positive after Cycle 6 defined as an IRF Deauville score of (4 or 5). This outcome measure was planned to be assessed only for participants treated in Phase 1 arm.
Measured: From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)
Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive
ATA positive was defined as participants who have a positive ATA in any postbaseline sample. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. Persistently ATA positive was defined as participants who have positive ATA in more than 2 postbaseline timepoints. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. nATA positive was defined as participants who have at least one positive nATA in any postbaseline ATA positive sample. Here, percentage of participants who were transiently or persistently ATA positive are considered as ATA positive. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Up to 7 months
Phase 2: Progression-free Survival (PFS)
PFS per IRF:time from first dose until disease progression per IRF/death due to any cause,whichever occurred first.Participants with no objective progressive disease (PD),did not die,were still on study follow-up at time of analysis were removed from study prior to documentation of PD,PFS was censored on date of last adequate disease assessment before initiation of any non-protocol,alternative therapy.Participants who were on antitumor treatment,other than SCT/radiotherapy,censoring was at last adequate disease assessment before initiation of such alternative treatment.If participant experienced disease progression per IRF/died after initiation of antitumor treatment,other than SCT/radiotherapy,such participant was censored and not considered having PFS.Outcome measure was planned to be assessed for all participant treated at recommended dose in Phase 2.As per SAP,Phase 2 data was summarized and reported in two arms:Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Event-free Survival (EFS)
EFS:Time from first dose until any treatment failure:PD per IRF including progression events during follow-up period,failing to complete 6 cycles of treatment due to any reason or death due to any cause,whichever occurred first.EFS per IRF were censored on last adequate disease assessment date per IRF if none of above events occur during study.Participants with antitumor treatment,other than SCT/radiotherapy as part of frontline treatment were censored at last adequate disease assessment before initiation of such alternative treatment.If a participant experienced disease progression per IRF/died after initiation of antitumor treatment,other than SCT/radiotherapy,such participant was censored,and not be considered having EFS.This outcome measure was planned to be assessed for all patients treated at recommended dose in Phase 2.As prespecified in SAP,data for Phase 2 was summarized and reported in two arms:Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Overall Survival (OS)
Overall survival was defined as time from first dose until death. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive, including study closure. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Duration of Response (DOR)
DOR per IRF in participants with a response (CR or PR per IRF) was defined as the time from start of the first objective tumor response (CR or PR per IRF) to the first subsequent PD or death due to any cause, whichever occurred first. For patients who did not have an objective PD, did not die and are either still on a study follow-up at the time of the analysis, or were removed from the study prior to documentation of PD, DOR has been censored on the date of last adequate disease assessment. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Phase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive
ATA positive was defined as participants who have a positive ATA in any postbaseline sample. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. Persistently ATA positive was defined as participants who have positive ATA in more than 2 postbaseline timepoints. Transiently ATA positive was defined as participants who have positive ATA in 1 or 2 postbaseline samples. nATA positive was defined as participants who have at least one positive nATA in any postbaseline ATA positive sample. Here, percentage of participants who were transiently or persistently ATA positive are considered as ATA positive. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: From first dose until 30 days after the last dose of study drug (up to 7 months)
Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Mean Plasma Cmax of MMAE
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Mean Plasma AUC0-15 of MMAE
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Median Tmax of MMAE in Plasma
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy
Peripheral Neuropathy (PN) was defined by the peripheral neuropathy standardized MedDRA query (SMQ) broad search. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events
Time to onset of first event was defined as time from first dose of study drug to onset of first treatment-emergent PN event. Time to resolution was calculated as the time from onset date to the date of resolution PN (SMQ) event. Participants with multiple resolved events were counted once at the longest time to resolution. Resolution was defined as an event outcome of resolved or resolved with sequelae. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT)
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline and End of Treatment (Month 7)
Phase 1: Percentage of Participants With Low and High ATA Titer Values
High ATA titer was defined as participants who have at least one postbaseline ATA titer less than (>) 25. Low ATA titer was defined as participants whose postbaseline ATA titer are all less than or equal to (<=) 25. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Up to 6 months
Phase 2: Percentage of Participants With Low and High ATA Titer Values
High ATA titer was defined as participants who have at least one postbaseline ATA titer >25. Low ATA titer was defined as participants whose postbaseline ATA titer are all <=25. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Up to 6 months
Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The data is reported per ATA status as categories. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Up to 24 months
Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Measured: Up to 24 months
Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Cycle 1-3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Cycle 1-3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
CR is defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Up to 24 months
Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT)
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin A at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline in Tetanus at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline in Haemophilus Influenzae B Antibody, IgG at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline Poliovirus Antibodies Ratio at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline Total Immunoglobulin at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline in Peripheral Blood CD34+A at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline in Total Lymphocyte Count at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD4+ (CD4+CD45RA-CD197- and CD4+CD45RA+CD197+) Subset of Cells at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Phase 2: Immune Reconstitution-Change From Baseline in the Percentage of CD8+ (CD8+CD45RA-CD197- and CD8+CD45RA-CD197+) Subset of Cells at EOT
This outcome measure was planned to be assessed only for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Measured: Baseline, EOT [Month 7]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2016 (estimated)
- Study start6 Sep 2017
- Primary completion5 May 2020
- Study completion24 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hodgkin DiseaseStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02979522
- Sponsor's protocol ID
- C25004
- Other IDs
- 2015-004112-38, U1111-1171-0984, 2023-506415-18-00, 2023, 2015
- Status last verified
- Nov 2025
- First submitted
- 11 Nov 2016
- Last updated
- 10 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
Suri A, Mould DR, Song G, Kinley J, Venkatakrishnan K. Population Pharmacokinetics of Brentuximab Vedotin in Adult and Pediatric Patients With Relapsed/Refractory Hematologic Malignancies: Model-Informed Hypothesis Generation for Pediatric Dosing Regimens. J Clin Pharmacol. 2020 Dec;60(12):1585-1597. doi: 10.1002/jcph.1682. Epub 2020 Jun 28.
PubMed 32596842
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Patients With Advanced Stage Newly Diagnosed Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT02979522
- Acronym / sponsor ID
- C25004
- Conditions
- Hodgkin Disease
- Keywords
- Drug therapy, pediatric Hodgkin disease, frontline Hodgkin disease, advanced stage Hodgkin disease, pediatric lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 59 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 6 Sep 2017 (actual)
- Primary completion
- 5 May 2020 (actual)
- Study completion
- 24 Sep 2029 (estimated)
- First posted
- 1 Dec 2016 (estimated)
- Results
- Posted 1 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as confirm the recommended dose of brentuximab vedotin (ADCETRIS) in combination with a multiagent chemotherapy regimen, doxorubicin (Adriamycin), vinblastine, and dacarbazine, in pediatric participants with advanced stage newly diagnosed classical CD30+ Hodgkin Lymphoma (HL).
Detailed description
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat pediatric participants who have advanced stage, newly diagnosed, classical CD30+ HL. This study will assess the safety, tolerability, and anti-tumor activity, as well as recommended dose of brentuximab vedotin in combination with a multiagent chemotherapy regimen that is based on a current standard of care (SOC) first-line treatment regimen for newly diagnosed HL.
The study will enroll approximately 55 evaluable participants. The study will be conducted in 2 phases, Phase 1 and Phase 2. Phase 1 study will enroll at least 6 participants to determine the recommended dose. Once the recommended dose is identified additional participants will be enrolled into phase 2 so that the total number of evaluable participants will be at least 55, including participants treated at recommended dose in Phase 1. Participants will be enrolled to the following initial dose cohort with an option to explore a reduced dose cohort at 36 mg/m^2 if needed:
- Brentuximab vedotin 48 mg/m^2 in combination with doxorubicin, vinblastine, and dacarbazine.
This multi-center trial will be conducted in the United States, Italy, Brazil and Japan. The overall time to participate in this study is approximately 55 months, including the follow-up period. Participants will be followed for a maximum of 30 days following the last dose of protocol therapy for a follow-up assessment and will be followed for survival and disease status every 12 weeks for 12 months, and then every 24 weeks until death or study closure or for up to 2 years from the date of the last participant enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD | Experimental | Drug: Brentuximab vedotin, Drug: Doxorubicin, Drug: Vinblastine, Drug: DacarbazineBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. |
| Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD | Experimental | Drug: Brentuximab vedotin, Drug: Doxorubicin, Drug: Vinblastine, Drug: DacarbazineBrentuximab vedotin 48 mg/m^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2, and dacarbazine 375 mg/m^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Each participant must meet all the following inclusion criteria to be enrolled in the study:
- Histologically confirmed CD30+ classical HL.
- Advanced stage, newly diagnosed HL (Stage III and Stage IV disease).
- Treatment-naive HL.
- Have performance scores of greater than or equal to (>=) 50 for Lansky Play-performance or Karnofsky Performance Status.
Key exclusion criteria (14 listed)
- Nodular lymphocyte predominant HL.
- Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML.
- Any sensory or motor peripheral neuropathy.
- Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.
- Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks before the first study protocol therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brentuximab vedotinAlso: AdcetrisBrentuximab vedotin infusion | Drug | Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD, Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD |
| DoxorubicinAlso: AdriamycinDoxorubicin infusion | Drug | Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD, Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD |
| VinblastineVinblastine infusion | Drug | Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD, Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD |
| DacarbazineDacarbazine infusion | Drug | Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD, Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD |
Primary outcome
Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population
Time frame: From the first dose (Cycle 1) up to Day 56 (Cycle length=28 days)
The recommended dose was determined after considering all safety data in phase 1 and assessing for dose limiting toxicities (DLTs) which are defined as the dose range at which less than or equal to (<=) 1 of 6 evaluable participants experience DLT within the defined observation period (Cycle 1 + 28 days). This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Phase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
Time frame: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.
Phase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
Time frame: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, Is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, Is a congenital anomaly/birth defect, Is a medically important event.
Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit
Time frame: At end of treatment (EOT) visit 30 days after the last dose of study drug (at Month 7)
CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in the statistical analysis plan (SAP) , data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
Time frame: From first dose of study drug up to Cycle 2 Day 25 (Each Cycle length=28 days)
The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
PR was defined as regression of measurable disease and no new sites as assessed by IRF as per IWG criteria. Percentage of participants in the response-evaluable population who achieved a partial response based on the IRF assessment at the EOT visit based on the IWG criteria are reported. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Phase 2: Percentage of Participants Who Achieved an Overall Response Rate (ORR) Per IRF Assessment Per IWG Criteria at EOT Visit
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Overall response rate was defined as the percentage of participants with CR or PR as assessed by IRF using IWG criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new diseases. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose
Time frame: From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)
This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.
49 secondary outcomes
Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb)
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE)
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum
Time frame: Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Median Time to Reach Cmax (Tmax) of MMAE in Plasma
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Percentage of Participants Who Achieved a CR Per IRF Assessment Per IWG Criteria at EOT Visit
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Phase 1: Percentage of Participants Who Achieved a PR Per IRF Assessment Per IWG Criteria at EOT Visit
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Phase 1: Percentage of Participants Who Achieved an ORR Per IRF Assessment Per IWG Criteria at EOT Visit
Time frame: At EOT visit 30 days after the last dose of study drug (at Month 7)
Phase 1: Percentage of Participants Whose Disease Was PET Negative After 2 Cycles of Protocol Therapy Per IRF Assessment
Time frame: From first dose of study drug up to Cycle 2 (Each Cycle length=28 days)
Phase 1: Percentage of Participants Whose Disease Was PET Positive After 6 Cycles of Protocol Therapy Per IRF Assessment
Time frame: From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)
Phase 1: Percentage of Participants Who Were Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive
Time frame: Up to 7 months
Phase 2: Progression-free Survival (PFS)
Time frame: Up to 24 months
Phase 2: Event-free Survival (EFS)
Time frame: Up to 24 months
Phase 2: Overall Survival (OS)
Time frame: Up to 24 months
Phase 2: Duration of Response (DOR)
Time frame: Up to 24 months
Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment
Time frame: Up to 24 months
Phase 2: Percentage of Participants Who Experienced AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
Time frame: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Phase 2: Percentage of Participants Who Experienced SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy
Time frame: From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)
Phase 2: Percentage of Participants Who Were ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive
Time frame: From first dose until 30 days after the last dose of study drug (up to 7 months)
Phase 2: Mean Serum Cmax of Brentuximab Vedotin and TAb
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Mean Plasma Cmax of MMAE
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Mean Serum AUC0-15d of Brentuximab Vedotin and TAb
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Mean Plasma AUC0-15 of MMAE
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Median Tmax of Brentuximab Vedotin and TAb in Serum
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Median Tmax of MMAE in Plasma
Time frame: Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Percentage of Participants Who Experienced Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy
Time frame: Up to 24 months
Phase 2: Time to Onset and Resolution for All Peripheral Neuropathy Events
Time frame: Up to 24 months
Phase 2: Immune Reconstitution-Change From Baseline Immunoglobulin G Levels at End of Treatment (EOT)
Time frame: Baseline and End of Treatment (Month 7)
Phase 1: Percentage of Participants With Low and High ATA Titer Values
Time frame: Up to 6 months
Phase 2: Percentage of Participants With Low and High ATA Titer Values
Time frame: Up to 6 months
Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Time frame: Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Mean AUC 0-15d of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Time frame: Cycle 1 and 3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 1: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
Time frame: Up to 24 months
Phase 1: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
Time frame: Up to 24 months
Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Time frame: Cycle 1-3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants
Time frame: Cycle 1-3: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)
Phase 2: Percentage of Participants Achieving CR Per IRF Assessment Per IWG Criteria in ATA Positive and ATA Negative Participants
Time frame: Up to 24 months
Phase 2: Number of ATA Positive and ATA Negative Participants With AEs and SAEs
Time frame: Up to 24 months
Phase 2: Immune Reconstitution-Change From Baseline in Immunoglobulin M at the End of Treatment (EOT)
Time frame: Baseline, EOT [Month 7]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32596842Suri A, Mould DR, Song G, Kinley J, Venkatakrishnan K. Population Pharmacokinetics of Brentuximab Vedotin in Adult and Pediatric Patients With Relapsed/Refractory Hematologic Malignancies: Model-Informed Hypothesis Generation for Pediatric Dosing Regimens. J Clin Pharmacol. 2020 Dec;60(12):1585-1597. doi: 10.1002/jcph.1682. Epub 2020 Jun 28.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
14 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Brentuximab vedotin, Doxorubicin and Vinblastine in people with Hodgkin Disease, run by Takeda at 14 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 10 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Brazil, Italy, United States, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population (time frame: From the first dose (Cycle 1) up to Day 56 (Cycle length=28 days)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02979522, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2025; AzTrials last refreshed its copy on 8 Nov 2026.