Diffuse, Large B-Cell, LymphomaPhase 2GIOTTONCT02374424
Phase II Study With Ga101-DHAP as Induction Therapy in Relapsed/Refractory DLBCL Patients
A Phase 2 study testing GA101_DHAP in people with Diffuse, Large B-Cell, Lymphoma, run by Fondazione Italiana Linfomi - ETS at 10 sites in Italy.
Trial summary
Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Diffuse, Large B-Cell, Lymphoma
- What is being tested?
- GA101_DHAP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 10 sitesItaly
- Study dates
- 5 Nov 2014to 23 Jun 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18≥ Age < 65
- Relapsed/refractory disease after receiving one line of standard R-CHOP like chemotherapy
- Diffuse Large B-cell Lymphoma at relapse. The re-biopsy is particularly recommended if relapse is over 1 year from previous complete remission. If this is harmful for the patient, the patient can be enrolled if archival tumor sample and block from first diagnosis are available.
- Measurable and/or evaluable disease
- Any Ann Arbor stage and IPI group at relapse
- Performance status < 2 according to Eastern Cooperative Oncology Group (ECOG) scale unless due to lymphoma
Show all 26Show fewer
- No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)
- Adequate haematological counts: Absolute Neutrophil Count (ANC) > 1.5 x 109/L, Hgb > 10.5 g/dl (transfusion independent), Platelet count > 75 x 109/L (transfusion independent), with the exception of cytopenia due to lymphoma bone marrow involvement
- Normal liver function (ALP, AST, ALT, GGT, conjugated bilirubin total < 2 x ULN) if not related to lymphoma
- Normal kidney function (creatinine clearance >= 80 ml/min)
- Cardiac ejection fraction > 50% (MUGA scan or echocardiography)
- Normal lung function
- Absence of active infections
- Non peripheral neuropathy or active neurological non neoplastic disease of CNS
- Non major surgical intervention prior 3 months to randomization if not due to lymphoma and/or not other disease life-threatening that can compromise chemotherapy treatment
- Disease free of prior malignancies other than lymphoma for > 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
- Life expectancy > 6 months
- No psychiatric illness that precludes understanding concepts of the trial or signing ten informed consent
- Written informed consent
- Women must be:
- postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months)
- surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),
- abstinent (at the discretion of the investigator/per local regulations), or
- if sexually active, be practicing a highly effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. They must also be prepared to continue birth control measures for at least 18 months after terminating treatment.
- Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening
- Men must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug.
Who cannot join
- Diagnosis of Lymphoblastic Lymphoma, Burkitt Lymphoma, Non Hodgkin Lymphoma CD20 negative, Mantle Cell Lymphoma, Follicular Lymphoma, Primary Mediastinal Lymphoma
- Age ≥ 65 years
- Patients ineligible to high-dose chemotherapy
- Performance status > 2 according to ECOG scale if not due to lymphoma
- Patients who previously received GA101 (obinutuzumab) are excluded.
- Patient has known or suspected hypersensitivity or intolerance to Rituximab
Show all 23Show fewer
- Patient has received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in nontreatment studies is allowed, if it will not interfere with participation in this study.
- CNS disease (meningeal and/or brain involvement by lymphoma)
- History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
- Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology). Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing.
- Positive test results for hepatitis C (HCV antibody serology testing). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
- Known history of HIV seropositive status. For patients with unknown HIV status, HIV testing will be performed at screening if required by local regulations.
- Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
- Uncontrolled or severe cardiovascular disease including myocardial infarction within six months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
- Cardiac ejection fraction < 45% (MUGA scan or echocardiography)
- Creatinine clearance < 45 ml/min
- Presence of major neurological disorders
- Active infection
- Major surgical intervention prior 3 months to randomization if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment
- Prior malignancies other than lymphoma in the last 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
- Life expectancy < 6 months
- Any other coexisting medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.
- If female, the patient is pregnant or breast-feeding.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Italy10 sites
Ospedale di Bolzano, Reparto di Ematologia & CTMO
Bolzano, 39100
A.O. Universitaria Careggi
Florence, 50139
Ospedale dell'Angelo, U.O. Ematologia
Mestre, 30174
A.O. Universitaria Policlinico Di Modena
Modena, 41124
Ematologia Policlinico San Matteo
Pavia, 27100
AO di Perugia S. Maria della misericordia
Perugia, 06132
Ematologia Ospedale S.Camillo Forlanini
Roma, 00149
Policlinico Umberto I - Università "La Sapienza"
Roma, 00161
Ematologia e Trapianto Istituto Regina Elena IFO
Roma
Ospedale San Bortolo
Vicenza, VI, 36100
About this study
Official title: Phase II Study With Ga101-DHAP as Induction Therapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) Patients Before High-Dose Chemotherapy BEAM With Autologous Stem Cell Transplantation (ASCT)
Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.
Read the detailed description
This is a prospective, multicenter, single arm, phase II trial in young patients (18-65 years) affected by relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) at diagnosis,eligible to high-dose therapy.
Aim of the study is to assess whether the addition of GA101 to DHAP is more promising than standard R-DHAP, as induction therapy before high dose chemotherapy BEAM with ASCT with respect to response.
The study is designed primarily to evaluate the efficacy of GA101-DHAP in patients with DLBCL who have relapsed or are refractory to one chemotherapy regimen and secondarily to assess safety and capability to mobilize peripheral stem cells The study is designed with two stages and with stopping rules after the first stage. In particular, at the end of the first stage, the study will be stopped if the efficacy is too low or if the toxicity, measured during the drug administration period, is too high with respect to pre-defined thresholds. .
- Conditions
- Diffuse, Large B-Cell, Lymphoma
- Being tested
- GA101_DHAP
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GA101_DHAPDrug
Aim of the study is to assess whether the addition of GA101 to DHAP is more promising than standard R-DHAP, as induction therapy before high dose chemotherapy BEAM with ASCT with respect to response.
Scheme of treatment:
- GA101 1000 mg iv day 1, 8, 15 on first cycle (starting from cycle 2, GA101 1000 mg day 1)
- Cisplatin 100 mg/sqm iv day 1 of every cycles in 24-hours infusion
- Cytarabine 2000 mg/sqm in 3-hours infusion every 12 hours iv day 2 of every cycles
- Dexamethasone 40 mg day 1-4 of every cycles
- Pegfilgrastim 6 mg sc single dose 24 hours after the end of chemotherapy or G-CSF from day 4 till stem cell harvest during mobilization's course (II o III cycle GA101-DHAP)
- GA101 1000 mg iv 24 hours before apheresis as purging in vivo during second courses of therapy
| Study group | Role | What they receive |
|---|---|---|
| GA101_DHAP | Experimental | Patients receive: GA101-DHAP x 2, restaging, mobilization and collection of peripheral blood stem cells, + GA101-DHAP x 2, restaging with PET and CT and consolidation with BEAM and ASCT in patients in response (CR+PR).
During the treatment period of four cycles, all patients will receive a total of four 28-day courses of chemotherapy. Receives: Drug: GA101_DHAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.
Primary objective is to assess whether the treatment achieves an absolute increase of the CR proportion of at least 20% (from 30% to 50%) with respect to the standard treatment.
The complete response rate (CR) evaluated by PET scan after four cycles of GA101-DHAP before ASCT according to Cheson criteria.
Measured: 4 months
Secondary outcomes (6)
Overall Response Rate (ORR) prior to consolidation with BEAM and ASCT
A patient is defined as a responder if she/he has a complete or partial response, evaluated by PET/TC, after four cycles of GA101-DHAP
Measured: 2 years
Progression free survival (PFS) at 6 month after the end of treatment (EOT)
Measured from the date of starting salvage therapy to the date of disease progression, relapse or death from any cause. Responding patients and patients who are lost to follow up will be surveyed at their last assessment date.
Measured: 6 month
Overall Survival (OS) at 2 years after the EOT
Measured from the date of starting salvage therapy to the date of death from any cause. Patients alive at the time of the final analysis will be surveyed at the date of the last contact. For both PFS and OS minimum follow up time required for all patients will be 2 years.
Measured: 2 years
Toxicity: Severe, life-threatening, fatal (grade 3, 4 and 5) and/or serious adverse events
Severe, life-threatening, fatal (grade 3, 4 and 5) and/or serious adverse events are defined according to "Common Terminology Criteria for Adverse Events" (CTCAE), version 4.0. and adverse events of special interests (AESI)
Measured: 2 years
The hematopoietic cell mobilization
Mobilizing potential: amount of CD34 + stem cell collected /Kg
Measured: 2 years
Feasibility: the rate of patients actually proceeding to ASCT
Proportion of patients successfully completing ASCT
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2015 (estimated)
- Study start5 Nov 2014
- Primary completionFeb 2018
- Study completion23 Jun 2020
Why it stopped: Interim analysis planned as per protocol didn't provide positive outcome therefore enrollment was not reopened. However, the enrolled patients concluded therapy and continued into the follow-up phase. The study was closed only after LVLP.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse, Large B-Cell, LymphomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Italiana Linfomi - ETS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maurizio Martelli, MD, Principal investigator, Dipartimento di Biotecnologie Cellulari ed Ematologia, "La Sapienza" Roma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02374424
- Sponsor's protocol ID
- FIL_GA101_DHAP
- Acronym
- GIOTTO
- Status last verified
- Jun 2022
- First submitted
- 17 Feb 2015
- Last updated
- 6 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study With Ga101-DHAP as Induction Therapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) Patients Before High-Dose Chemotherapy BEAM With Autologous Stem Cell Transplantation (ASCT)
- ClinicalTrials.gov ID
- NCT02374424
- Acronym / sponsor ID
- GIOTTO / FIL_GA101_DHAP
- Conditions
- Diffuse, Large B-Cell, Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim analysis planned as per protocol didn't provide positive outcome therefore enrollment was not reopened. However, the enrolled patients concluded therapy and continued into the follow-up phase. The study was closed only after LVLP.
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Fondazione Italiana Linfomi - ETSUniversity, hospital or other
- Study start
- 5 Nov 2014 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- 23 Jun 2020 (actual)
- First posted
- 27 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.
Detailed description
This is a prospective, multicenter, single arm, phase II trial in young patients (18-65 years) affected by relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) at diagnosis,eligible to high-dose therapy.
Aim of the study is to assess whether the addition of GA101 to DHAP is more promising than standard R-DHAP, as induction therapy before high dose chemotherapy BEAM with ASCT with respect to response.
The study is designed primarily to evaluate the efficacy of GA101-DHAP in patients with DLBCL who have relapsed or are refractory to one chemotherapy regimen and secondarily to assess safety and capability to mobilize peripheral stem cells The study is designed with two stages and with stopping rules after the first stage. In particular, at the end of the first stage, the study will be stopped if the efficacy is too low or if the toxicity, measured during the drug administration period, is too high with respect to pre-defined thresholds. .
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GA101_DHAP | Experimental | Drug: GA101_DHAPPatients receive: GA101-DHAP x 2, restaging, mobilization and collection of peripheral blood stem cells, + GA101-DHAP x 2, restaging with PET and CT and consolidation with BEAM and ASCT in patients in response (CR+PR). During the treatment period of four cycles, all patients will receive a total of four 28-day courses of chemotherapy. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 18≥ Age < 65
- Relapsed/refractory disease after receiving one line of standard R-CHOP like chemotherapy
- Diffuse Large B-cell Lymphoma at relapse. The re-biopsy is particularly recommended if relapse is over 1 year from previous complete remission. If this is harmful for the patient, the patient can be enrolled if archival tumor sample and block from first diagnosis are available.
- Measurable and/or evaluable disease
- Any Ann Arbor stage and IPI group at relapse
Key exclusion criteria (23 listed)
- Diagnosis of Lymphoblastic Lymphoma, Burkitt Lymphoma, Non Hodgkin Lymphoma CD20 negative, Mantle Cell Lymphoma, Follicular Lymphoma, Primary Mediastinal Lymphoma
- Age ≥ 65 years
- Patients ineligible to high-dose chemotherapy
- Performance status > 2 according to ECOG scale if not due to lymphoma
- Patients who previously received GA101 (obinutuzumab) are excluded.
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 |
|---|---|---|
| GA101_DHAPAim of the study is to assess whether the addition of GA101 to DHAP is more promising than standard R-DHAP, as induction therapy before high dose chemotherapy BEAM with ASCT with respect to response. Scheme of treatment: * GA101 1000 mg iv day 1, 8, 15 on first cycle (starting from cycle 2, GA101 1000 mg day 1) * Cisplatin 100 mg/sqm iv day 1 of every cycles in 24-hours infusion * Cytarabine 2000 mg/sqm in 3-hours infusion every 12 hours iv day 2 of every cycles * Dexamethasone 40 mg day 1-4 of every cycles * Pegfilgrastim 6 mg sc single dose 24 hours after the end of chemotherapy or G-CSF from day 4 till stem cell harvest during mobilization's course (II o III cycle GA101-DHAP) * GA101 1000 mg iv 24 hours before apheresis as purging in vivo during second courses of therapy | Drug | GA101_DHAP |
Primary outcome
Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.
Time frame: 4 months
Primary objective is to assess whether the treatment achieves an absolute increase of the CR proportion of at least 20% (from 30% to 50%) with respect to the standard treatment. The complete response rate (CR) evaluated by PET scan after four cycles of GA101-DHAP before ASCT according to Cheson criteria.
6 secondary outcomes
Overall Response Rate (ORR) prior to consolidation with BEAM and ASCT
Time frame: 2 years
Progression free survival (PFS) at 6 month after the end of treatment (EOT)
Time frame: 6 month
Overall Survival (OS) at 2 years after the EOT
Time frame: 2 years
Toxicity: Severe, life-threatening, fatal (grade 3, 4 and 5) and/or serious adverse events
Time frame: 2 years
The hematopoietic cell mobilization
Time frame: 2 years
Feasibility: the rate of patients actually proceeding to ASCT
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Interim analysis planned as per protocol didn't provide positive outcome therefore enrollment was not reopened. However, the enrolled patients concluded therapy and continued into the follow-up phase. The study was closed only after LVLP.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2022.
- Individual participant dataSharing planned: No
Related trials for Diffuse, Large B-Cell, Lymphoma
RecruitingPhase 1
Testing the Combination of Anti-cancer Drugs Mosunetuzumab, Polatuzumab Vedotin, and Lenalidomide for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High Grade B-Cell Lymphoma
Active, not recruitingPhase 2
Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma
Ann Arbor Stage II Diffuse Large B-Cell Lymphoma, Ann Arbor Stage III Diffuse Large B-Cell Lymphoma
RecruitingPhase 1
KSV01 Injection for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma (DLBCL)
Active, not recruitingPhase 1
Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic Leukemia
B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma, B-Cell Prolymphocytic Leukemia
RecruitingPhase 1
HEME-25 Open-Label Feasibility Study of Elranatamab Utilized as Consolidation in Newly Diagnosed Plasmablastic Lymphoma With or Without HIV
Plasmablastic Lymphoma, HIV
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.
Maurizio Martelli, MD principal investigator
Dipartimento di Biotecnologie Cellulari ed Ematologia, "La Sapienza" Roma
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GA101_DHAP in people with Diffuse, Large B-Cell, Lymphoma, run by Fondazione Italiana Linfomi - ETS at 10 sites in Italy.
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 26 inclusion and 23 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: stopped early, as of the sponsor's last update on 6 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Italy. 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 phase mean?
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?
The study was stopped early (reason given: Interim analysis planned as per protocol didn't provide positive outcome therefore enrollment was not reopened. However, the enrolled patients concluded therapy and continued into the follow-up phase. The study was closed only after LVLP.). Results are not available in the source record.
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?
Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL. (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jun 2022.