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Precursor Cell Lymphoblastic Leukemia-LymphomaPhase 2NCT03384654

A Study to Evaluate the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Participants Greater Than or Equal to (>=)1 and Less Than or Equal to (<=) 30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

A Phase 2 study testing Daratumumab, Vincristine and Prednisone in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma, run by Janssen Research & Development, LLC at 53 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the efficacy of daratumumab in addition to standard chemotherapy in pediatric participants with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LL) and T-cell ALL/LL as measured by the complete response (CR) rate. Read more about this study

Who is it for?
Ages 1 year to 30 years
What is being tested?
Daratumumab, Vincristine and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
53 sitesin 10 countries
Study dates
14 May 2018to 27 Sep 2022
Phase
Phase 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 1 year to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Documented acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) as defined by the criteria below:
  • B-cell cohort: Stage 1; ALL in second or greater relapse or refractory to 2 prior induction regimens with greater than or equal to (>=) 5 percent (%) blasts in the bone marrow and aged 1 to less than (<) 18 years. Stage 2; ALL in second or greater relapse or refractory to 2 prior induction regimens with (>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in second or greater relapse or refractory to 2 prior induction regimens and biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years.
  • T-cell cohort: Stage 1; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (>=) 5% blasts in the bone marrow and aged 1 to <18 years. Stage 2; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in first relapse or refractory to 1 prior induction/consolidation regimen biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years
  • Performance status greater than or equal to (>=) 70 by Lansky scale (for participants less than [<] 16 years of age) or Karnofsky scale (for participants [>=] 16 years of age)
  • Adequate hematology laboratory values at Cycle 1 Day 1 pre-dosing defined as follows:
  • Hemoglobin (>=) 7.5 gram per deciliter (g/dL) ([>=] 5 millimole per liter [mmol/L]; prior red blood cell [RBC] transfusion is permitted)
Show all 12Show fewer
  • Platelet count (>=) 10*10^9 per liter (L) (prior platelet transfusion is permitted)
  • Adequate renal function defined as normal serum creatinine for the participant's age or creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) prior to enrollment
  • Adequate liver function prior to enrollment defined as:
  • Alanine aminotransferase level less than or equal to (<=) 2.5* the upper limit of normal (ULN),
  • Aspartate aminotransferase level (<=) 2.5* ULN, and
  • Total bilirubin (<=) 2* ULN or direct bilirubin level (<=) 2.0* ULN

Who cannot join

  • Received an allogeneic hematopoietic transplant within 3 months of screening
  • Active acute graft-versus-host disease of any grade or chronic graft-versus-host disease of Grade 2 or higher
  • Received immunosuppression post hematopoietic transplant within 1 month of study entry
  • Philadelphia chromosome positive (Ph+) B-cell ALL eligible for tyrosine kinase inhibitor therapy
  • Has either of the following:
  • Evidence of dyspnea at rest or oxygen saturation (<=) 94 percent (%).
Show all 12Show fewer
  • Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
  • Received an investigational drug, was vaccinated with live attenuated vaccines, or used an invasive investigational medical device within 4 weeks before the planned first dose of study drug, or is currently being treated in an investigational study
  • Known to be seropositive for human immunodeficiency virus (HIV)
  • Any one of the following:
  • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
  • Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)

Trial locations and contacts

53 sites in 10 countries.

53 sites in 10 countries

United States26 sites

  • C.S. Mott Children's Hospital

    Ann Arbor, Michigan, 48109-4257

  • Children'S Healthcare Of Atlanta/Emory Univ. Dept. Of Pediatrics

    Atlanta, Georgia, 30342

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas/Children's Blood and Cancer Center

    Austin, Texas, 78723

  • Johns Hopkins University

    Baltimore, Maryland, 21231-1000

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233-1711

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215-5418

  • Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Nationwide Children's Hospital

    Columbus, Ohio, 43214

  • UT Southwestern Medical Center

    Dallas, Texas, 75235

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Medical College Of Wisconsin

    Milwaukee, Wisconsin, 53226-3522

  • New York University Langone Medical Center

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

  • Children's Hospital Orange County

    Orange, California, 92868

  • Stanford University

    Palo Alto, California, 94304

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • University of Utah Primary Children's Medical Center

    Salt Lake City, Utah, 84113

  • Washington Univeristy School of Medicine/ Pediatrics

    St Louis, Missouri, 63110

  • Stony Brook University Medical Center

    Stony Brook, New York, 11733

Other trials in United States

United Kingdom7 sites

  • Bristol Royal Hospital for Children

    Bristol, BS2 8BJ

  • Royal Hospital for Sick Children

    Glasgow, G51 4TF

  • Leeds Children's Hospital

    Leeds, LS1 3EX

  • University College London Hospitals

    London, NW1 2BU

  • Great Ormond Street Hospital

    London, WC1N 2JH

  • Royal Manchester Children's Hospital

    Manchester, M13 9WL

  • Royal Marsden Hospital

    Surrey, SM2 5PT

Other trials in United Kingdom

France5 sites

  • CHU de Bordeaux, Hopital des Enfants

    Bordeaux, 33076

  • IHOPE - Hospices civils de Lyon

    Lyon, 69008

  • Hopital trousseau- APHP

    Paris, 75012

  • Hôpital Robert Debré

    Paris, 75019

  • Hôpital D'Enfants

    Vandœuvre-lès-Nancy, 54500

Other trials in France

Italy4 sites

  • Istituto Giannina Gaslini

    Genova, 16147

  • Fondazione MBBM, ASST Monza

    Monza, 20900

  • Ospedale Pediatrico Bambin Gesù

    Roma, 00165

  • AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita

    Torino, 10126

Other trials in Italy

Spain4 sites

  • Hosp Univ Vall D Hebron

    Barcelona, 8035

  • Hosp. Sant Joan de Deu

    Esplugues de Llobregat, 08950

  • Hosp. Infantil Univ. Nino Jesus

    Madrid, 28009

  • Hosp. Univ. I Politecni La Fe

    Valencia, 46026

Other trials in Spain

Germany3 sites

  • Charite-Universitätsmedizin Berlin - Berlin

    Berlin, 13353

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitatsklinikum Munster

    Münster, 48149

Other trials in Germany

Belgium1 site

  • Universitair Ziekenhuis Gent - UZ GENT

    Ghent, 9000

Other trials in Belgium

Israel1 site

  • Schneider Children's Medical Center

    Petach Tiquva, 4920235

Other trials in Israel

Netherlands1 site

  • Princess Maxima Center

    Utrecht, 3584 EA

Other trials in Netherlands

Sweden1 site

  • Karolinska University Hospital

    Stockholm, 17176

Other trials in Sweden

About this study

Official title: An Open-label, Multicenter, Phase 2 Study Evaluating the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Subjects >=1 and <=30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

The purpose of this study is to evaluate the efficacy of daratumumab in addition to standard chemotherapy in pediatric participants with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LL) and T-cell ALL/LL as measured by the complete response (CR) rate.

Read the detailed description

Screening for eligible participants will be performed within 21 days before administration of the study drug. Participants with B-cell ALL/LL will receive treatment until disease progression, unacceptable toxicity or achievement of CR followed by hematopoietic stem cell transplant (HSCT). Participants with T cell ALL/LL will receive treatment for up to 2 cycles. If disease progression is confirmed, then the participant will discontinue study treatment, complete the End of Treatment Visit, and enter the Posttreatment Period. For those participants who discontinue study drug prior to disease progression, disease evaluations will continue to be performed every 8 weeks until subsequent anticancer therapy is initiated.

Being tested
Daratumumab, Vincristine, Prednisone, Doxorubicin, Peg-asparaginase
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaratumumabDrug

    Participant will receive daratumumab 16 milligram per kilogram (mg/kg) in cohort 1 and cohort 2.

  • VincristineDrug

    Participant will receive vincristine 1.5 milligram per meter square (mg/m^2) in cohort 1 and cohort 2.

  • PrednisoneDrug

    Participant will receive prednisone 40 mg/m^2 in cohort 1 and cohort 2.

  • DoxorubicinDrug

    Participant will receive doxorubicin 60 mg/m^2 in cohort 2.

  • Peg-asparaginaseBiological

    Participant will receive peg-asparaginase 2500 units per meter square (U/m^2) in cohort 2.

  • CyclophosphamideDrug

    Participant will receive cyclophosphamide 1 gram per meter square (g/m^2) once in cohort 2.

  • CytarabineDrug

    Participant will receive cytarabine 75 mg/m^2 in cohort 2.

  • 6-mercaptopurineDrug

    Participant will receive 6-mercaptopurine 60 mg/m^2 orally daily in cohort 2.

  • MethotrexateDrug

    Participant will receive methotrexate 5 g/m^2 intravenously (IV) in cohort 2.

Study groups in NCT03384654
Study groupRoleWhat they receive
Cohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LLExperimentalCohort 1 will include participants with B cell ALL/LL in second or greater relapse or refractory to at least 2 prior induction regimens. Participant will receive daratumumab in combination with vincristine and prednisone.
Receives: Drug: Daratumumab; Drug: Vincristine; Drug: Prednisone
Cohort 2: T-Cell ALL/LLExperimentalCohort 2 will include participants with T-cell ALL/LL in first relapse or refractory to at least 1 prior induction/consolidation regimen. Participant will receive daratumumab in combination with vincristine, prednisone, doxorubicin and peg-asparaginase in Cycle 1 and daratumumab in combination with cyclophosphamide, cytarabine, 6- mercaptopurine and methotrexate in Cycle 2.
Receives: Drug: Daratumumab; Drug: Vincristine; Drug: Prednisone; Drug: Doxorubicin; Biological: Peg-asparaginase; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: 6-mercaptopurine; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cohort 1: Percentage of Participants With Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL)

    Complete response based on the modified National Comprehensive Cancer Network (NCCN) criteria was defined as: less than 5 percent (%) blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets greater than (>)100*10^9 cells/liter (L) and absolute neutrophil count (ANC) >1.0*10^9 cells/L. This outcome measure was planned to be analyzed for specified arm only.

    Measured: Up to 2 cycles, that is, up to 56 days (each cycle of 28-days)

  2. Cohort 2: Percentage of Participants With Complete Response (CR) for T-cell ALL

    Complete response based on the modified NCCN criteria was defined as: less than 5% blasts in the bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets >100*10^9 cells/L and ANC >1.0*10^9 cells/L. This outcome measure was planned to be analyzed for specified arms only.

    Measured: End of Cycle 1 (that is, up to 28 days)

Secondary outcomes (10)

  1. Overall Response Rate (ORR)

    For ALL participants, ORR was defined as percentage of participants who achieved CR or CR with only partial hematological recovery(CRi) as per NCCN criteria. CR for ALL: less than 5% blasts in bone marrow; no evidence of circulating blasts or extramedullary disease; full recovery of peripheral blood counts: platelets >100*10^9 cells/L and ANC >1.0*10^9 cells/L. CRi for ALL: less than 5% blasts in bone marrow; no evidence of circulating blasts or extramedullary disease; partial recovery of peripheral blood counts not meeting criteria for CR. For LL participants, ORR was defined as percentage of participants who had CR or PR during or after treatment administration but prior to start of subsequent anti-cancer therapy or allogeneic hematopoietic stem cell transplant(HSCT). CR for LL: disappearance of all evidence of disease from all sites. PR for LL: decrease of >=50% in sum of products of diameter of lesions of up to 6 of largest dominant nodes or nodal masses with no new lesions.

    Measured: Up to 4 years 4 months

  2. Event-free Survival (EFS)

    EFS was defined as the time (in months) from the date of first treatment to the first documented treatment failure (that is [ie], disease progression) or date of relapse from CR or death due to any cause, whichever occurred first. Per NCCN criteria, relapse from CR is defined as: reappearance of leukemia blasts in the peripheral blood or >5% blasts in the bone marrow; reappearance of extramedullary disease or new extramedullary disease. Progressive disease: increase of at least 25% in the absolute number of circulating peripheral or bone marrow blasts, or development of new extramedullary disease. Kaplan-Meier method was used for the analysis.

    Measured: Up to 4 years 4 months

  3. Relapse-free Survival (RFS)

    RFS was defined as the time (in months) from CR to relapse from CR, or disease progression or death due to any cause, whichever occurred first. For ALL, as per NCCN criteria, relapse from CR is defined as: reappearance of leukemia blasts in the peripheral blood or >5% blasts in the bone marrow, or reappearance of extramedullary disease or new extramedullary disease. Progressive disease: increase of at least 25% in absolute number of circulating peripheral or bone marrow blasts, or development of new extramedullary disease. Kaplan-Meier method was used for analysis.

    Measured: Up to 4 years 4 months

  4. Overall Survival (OS)

    OS was defined as the time (in months) from the date of first study drug administration to the date of death due to any cause. Kaplan-Meier method was used for the analysis. Participants who died after consent withdrawal were considered as having an OS event.

    Measured: Up to 4 years 4 months

  5. Minimal Residual Disease (MRD) Negative Rate

    MRD negative rate was defined as the percentage of participants who were considered MRD negative after MRD testing by bone marrow aspirate at any timepoint after first study treatment administration and before disease progression or starting subsequent anti-cancer therapy or allogeneic hematopoietic stem cell transplant (HSCT). MRD negative was defined as less than (<) 0.01% abnormal population counts to nucleated mononuclear cells when measured by flow cytometry.

    Measured: Up to 4 years 4 months

  6. Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

    Percentage of participants who received an allogeneic HSCT after treatment with daratumumab were reported.

    Measured: Up to 4 years 4 months

  7. Maximum Observed Serum Concentration (Cmax) of Daratumumab

    Cmax was defined as maximum observed serum concentration of daratumumab.

    Measured: Cohort 1: B-cell ALL: End of infusion (EOI) on Day 1 of Cycle 2; Cohort 2: T-cell ALL (1-17 years): EOI on Day 22 of Cycle 2; Cohort 2: T-cell ALL (18-30 years): EOI on Day 1 of Cycle 2; Cohort 2: T-cell LL (1-30 years): EOI on Day 22 of Cycle 2

  8. Minimum Observed Serum Concentration (Cmin) of Daratumumab

    Cmin was defined as minimum observed serum concentration of daratumumab.

    Measured: Cohort 1: B-cell ALL: Predose on Day 1 of Cycle 2; Cohort 2: T-cell ALL (1-17 years): Predose on Day 22 of Cycle 2; Cohort 2: T-cell ALL (18-30 years): Predose on Day 1 of Cycle 2; Cohort 2: T-cell LL (1-30 years): Predose on Day 22 of Cycle 2

  9. Number of Participants With Anti-daratumumab Antibodies

    Number of participants with anti-daratumumab antibodies was reported.

    Measured: Up to 4 years 4 months

  10. Concentration of Daratumumab in Cerebrospinal Fluid (CSF)

    Concentration of daratumumab in CSF was reported. '0' in the number analyzed field signifies that none of the participants were available for the analysis at the specified time points.

    Measured: Pre-dose on Cohort 1: Cycles 1 and 2: Day 1; Cohort 2: Cycle 1 Day 1 and Day 15 and Cycle 2 Day 2 and Day 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Dec 2017
  2. Study start14 May 2018
  3. Primary completion22 Sep 2022
  4. Study completion27 Sep 2022

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03384654
Sponsor's protocol ID
CR108432
Other IDs
2017-003377-34, 54767414ALL2005, 2017
Status last verified
May 2025
First submitted
20 Dec 2017
Last updated
25 May 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Bhatla T, Hogan LE, Teachey DT, Bautista F, Moppett J, Velasco Puyo P, Micalizzi C, Rossig C, Shukla N, Gilad G, Locatelli F, Baruchel A, Zwaan CM, Bezler NS, Rubio-San-Simon A, Taussig DC, Raetz EA, Mao ZJ, Wood BL, Alvarez Arias D, Krevvata M, Nnane I, Bandyopadhyay N, Lopez Solano L, Dennis RM, Carson R, Vora A. Daratumumab in pediatric relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma: the DELPHINUS study. Blood. 2024 Nov 21;144(21):2237-2247. doi: 10.1182/blood.2024024493.

    PubMed 39158071

  • Ruhayel SD, Valvi S. Daratumumab in T-cell acute lymphoblastic leukaemia: A case report and review of the literature. Pediatr Blood Cancer. 2021 May;68(5):e28829. doi: 10.1002/pbc.28829. Epub 2020 Nov 27. No abstract available.

    PubMed 33245179

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab, Vincristine and Prednisone in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma, run by Janssen Research & Development, LLC at 53 sites in 10 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 12 inclusion and 12 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: finished, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States, United Kingdom, France, Italy, Spain and 5 more countries. 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?

Yes. Results are posted in the registry (first posted 13 Oct 2023). 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?

Cohort 1: Percentage of Participants With Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL) (time frame: Up to 2 cycles, that is, up to 56 days (each cycle of 28-days)). The study lists 2 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 NCT03384654, which also lists 2 linked publications.

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 25 May 2025.

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