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

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.

Study Overview

• Status: Completed
• Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Intervention / Treatment: Drug: Daratumumab; Drug: Vincristine; Drug: Prednisone; Drug: Doxorubicin; Biological: Peg-asparaginase; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: 6-mercaptopurine; Drug: Methotrexate

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent - UZ GENT
• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux, Hopital des Enfants
  • Lyon, France, 69008
    • IHOPE - Hospices civils de Lyon
  • Paris, France, 75019
    • Hopital Robert Debre
  • Paris, France, 75012
    • Hopital trousseau- APHP
  • Vandoeuvre les Nancy, France, 54500
    • Hôpital D'Enfants
• Germany
  • Berlin, Germany, 13353
    • Charite-Universitätsmedizin Berlin - Berlin
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
• Israel
  • Petach Tiquva, Israel, 4920235
    • Schneider Children's Medical Center
• Italy
  • Genova, Italy, 16147
    • Istituto Giannina Gaslini
  • Monza, Italy, 20900
    • Fondazione MBBM, ASST Monza
  • Roma, Italy, 00165
    • Ospedale Pediatrico Bambin Gesù
  • Torino, Italy, 10126
    • AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita
• Netherlands
  • Utrecht, Netherlands, 3584 EA
    • Princess Máxima Center
• Spain
  • Barcelona, Spain, 8035
    • Hosp Univ Vall D Hebron
  • Esplugues de Llobregat, Spain, 08950
    • Hosp. Sant Joan de Deu
  • Madrid, Spain, 28009
    • Hosp. Infantil Univ. Nino Jesus
  • Valencia, Spain, 46026
    • Hosp. Univ. I Politecni La Fe
• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital
• United Kingdom
  • Bristol, United Kingdom, BS2 8BJ
    • Bristol Royal Hospital for Children
  • Glasgow, United Kingdom, G51 4TF
    • Royal Hospital for Sick Children
  • Leeds, United Kingdom, LS1 3EX
    • Leeds Children's Hospital
  • London, United Kingdom, NW1 2BU
    • University College London Hospitals
  • London, United Kingdom, WC1N 2JH
    • Great Ormond Street Hospital
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
  • Surrey, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-1711
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
    • Orange, California, United States, 92868
      • Children's Hospital Orange County
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children'S Healthcare Of Atlanta/Emory Univ. Dept. Of Pediatrics
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Maryland
    • Baltimore, Maryland, United States, 21231-1000
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-5418
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-4257
      • C.S. Mott Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Univeristy School of Medicine/ Pediatrics
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • Stony Brook, New York, United States, 11733
      • Stony Brook University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43214
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas/Children's Blood and Cancer Center
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah Primary Children's Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3522
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) as defined by the criteria below:

  1. 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.
  2. 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:

  1. Hemoglobin (>=) 7.5 gram per deciliter (g/dL) ([>=] 5 millimole per liter [mmol/L]; prior red blood cell [RBC] transfusion is permitted)
  2. 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:

  1. Alanine aminotransferase level less than or equal to (<=) 2.5* the upper limit of normal (ULN),
  2. Aspartate aminotransferase level (<=) 2.5* ULN, and
  3. Total bilirubin (<=) 2* ULN or direct bilirubin level (<=) 2.0* ULN

Exclusion Criteria:

• 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:

  1. Evidence of dyspnea at rest or oxygen saturation (<=) 94 percent (%).
  2. 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:

  1. 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
  2. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL; Cohort 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.	Drug: Daratumumab; Participant will receive daratumumab 16 milligram per kilogram (mg/kg) in cohort 1 and cohort 2.; Drug: Vincristine; Participant will receive vincristine 1.5 milligram per meter square (mg/m^2) in cohort 1 and cohort 2.; Drug: Prednisone; Participant will receive prednisone 40 mg/m^2 in cohort 1 and cohort 2.
Experimental: Cohort 2: T-Cell ALL/LL; Cohort 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.	Drug: Daratumumab; Participant will receive daratumumab 16 milligram per kilogram (mg/kg) in cohort 1 and cohort 2.; Drug: Vincristine; Participant will receive vincristine 1.5 milligram per meter square (mg/m^2) in cohort 1 and cohort 2.; Drug: Prednisone; Participant will receive prednisone 40 mg/m^2 in cohort 1 and cohort 2.; Drug: Doxorubicin; Participant will receive doxorubicin 60 mg/m^2 in cohort 2.; Biological: Peg-asparaginase; Participant will receive peg-asparaginase 2500 units per meter square (U/m^2) in cohort 2.; Drug: Cyclophosphamide; Participant will receive cyclophosphamide 1 gram per meter square (g/m^2) once in cohort 2.; Drug: Cytarabine; Participant will receive cytarabine 75 mg/m^2 in cohort 2.; Drug: 6-mercaptopurine; Participant will receive 6-mercaptopurine 60 mg/m^2 orally daily in cohort 2.; Drug: Methotrexate; Participant will receive methotrexate 5 g/m^2 intravenously (IV) in cohort 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 cycles, that is, up to 56 days (each cycle of 28-days)
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.	End of Cycle 1 (that is, up to 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 4 years 4 months
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.	Up to 4 years 4 months
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.	Up to 4 years 4 months
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.	Up to 4 years 4 months
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.	Up to 4 years 4 months
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.	Up to 4 years 4 months
Maximum Observed Serum Concentration (Cmax) of Daratumumab	Cmax was defined as maximum observed serum concentration of daratumumab.	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
Minimum Observed Serum Concentration (Cmin) of Daratumumab	Cmin was defined as minimum observed serum concentration of daratumumab.	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
Number of Participants With Anti-daratumumab Antibodies	Number of participants with anti-daratumumab antibodies was reported.	Up to 4 years 4 months
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.	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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2018
• Primary Completion (Actual): September 22, 2022
• Study Completion (Actual): September 27, 2022

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 27, 2017

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Lymphoma; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Antirheumatic Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Methotrexate; Prednisone; Cyclophosphamide; Cytarabine; Doxorubicin; Vincristine; Asparaginase; Pegaspargase; Daratumumab; Mercaptopurine
• Other Study ID Numbers: CR108432; 2017-003377-34 (EudraCT Number); 54767414ALL2005 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No