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

NCT03384654 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CR1084322017-003377-3454767414ALL2005
• Study Type: interventional
• Target: 47
• Locations: 10 countries
• Sites: 53

Brief 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.

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Overall Response Rate (ORR)

  Up to 4 years 4 months

• Event-free Survival (EFS)

  Up to 4 years 4 months

• Relapse-free Survival (RFS)

  Up to 4 years 4 months

• Overall Survival (OS)

  Up to 4 years 4 months

• Minimal Residual Disease (MRD) Negative Rate

  Up to 4 years 4 months

Study Arms (2)

Cohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL

EXPERIMENTAL

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; Drug: Vincristine; Drug: Prednisone

Cohort 2: T-Cell ALL/LL

EXPERIMENTAL

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; Drug: Vincristine; Drug: Prednisone; Drug: Doxorubicin; Biological: Peg-asparaginase; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: 6-mercaptopurine; Drug: Methotrexate

Interventions

Daratumumab DRUG

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

Cohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL; Cohort 2: T-Cell ALL/LL

Vincristine DRUG

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

Cohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL; Cohort 2: T-Cell ALL/LL

Prednisone DRUG

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

Cohort 1: B-Cell Acute Lymphoblastic Leukemia (ALL)/LL; Cohort 2: T-Cell ALL/LL

Doxorubicin DRUG

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

Cohort 2: T-Cell ALL/LL

Peg-asparaginase BIOLOGICAL

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

Cohort 2: T-Cell ALL/LL

Cyclophosphamide DRUG

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

Cohort 2: T-Cell ALL/LL

Cytarabine DRUG

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

Cohort 2: T-Cell ALL/LL

6-mercaptopurine DRUG

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

Cohort 2: T-Cell ALL/LL

Methotrexate DRUG

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

Cohort 2: T-Cell ALL/LL

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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 (%).
• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (53)

University of Alabama at Birmingham

Birmingham, Alabama, 35233-1711, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Children's Hospital Orange County

Orange, California, 92868, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

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

Atlanta, Georgia, 30342, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231-1000, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5418, United States

Location

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109-4257, United States

Location

Washington Univeristy School of Medicine/ Pediatrics

St Louis, Missouri, 63110, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11733, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43214, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

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

Austin, Texas, 78723, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

Medical College Of Wisconsin

Milwaukee, Wisconsin, 53226-3522, United States

Location

Universitair Ziekenhuis Gent - UZ GENT

Ghent, 9000, Belgium

Location

CHU de Bordeaux, Hopital des Enfants

Bordeaux, 33076, France

Location

IHOPE - Hospices civils de Lyon

Lyon, 69008, France

Location

Hopital trousseau- APHP

Paris, 75012, France

Location

Hôpital Robert Debré

Paris, 75019, France

Location

Hôpital D'Enfants

Vandœuvre-lès-Nancy, 54500, France

Location

Charite-Universitätsmedizin Berlin - Berlin

Berlin, 13353, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitatsklinikum Munster

Münster, 48149, Germany

Location

Schneider Children's Medical Center

Petach Tiquva, 4920235, Israel

Location

Istituto Giannina Gaslini

Genova, 16147, Italy

Location

Fondazione MBBM, ASST Monza

Monza, 20900, Italy

Location

Ospedale Pediatrico Bambin Gesù

Roma, 00165, Italy

Location

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

Torino, 10126, Italy

Location

Princess Maxima Center

Utrecht, 3584 EA, Netherlands

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Sant Joan de Deu

Esplugues de Llobregat, 08950, Spain

Location

Hosp. Infantil Univ. Nino Jesus

Madrid, 28009, Spain

Location

Hosp. Univ. I Politecni La Fe

Valencia, 46026, Spain

Location

Karolinska University Hospital

Stockholm, 17176, Sweden

Location

Bristol Royal Hospital for Children

Bristol, BS2 8BJ, United Kingdom

Location

Royal Hospital for Sick Children

Glasgow, G51 4TF, United Kingdom

Location

Leeds Children's Hospital

Leeds, LS1 3EX, United Kingdom

Location

University College London Hospitals

London, NW1 2BU, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 2JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Royal Marsden Hospital

Surrey, SM2 5PT, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 39158071 DERIVED

• 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.

  PMID: 33245179 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

daratumumab; Vincristine; Prednisone; Doxorubicin; pegaspargase; Cyclophosphamide; Cytarabine; Mercaptopurine; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines; Aminopterin; Pterins; Pteridines

Results Point of Contact

• Title: Global Medical Head
• Organization: Janssen-Cilag International NV

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: December 27, 2017
• Study Start: May 14, 2018
• Primary Completion: September 22, 2022
• Study Completion: September 27, 2022
• Last Updated: May 25, 2025
• Results First Posted: October 13, 2023

Record last verified: 2025-05

Locations

NL (1); DE (3); IL (1); IT (4); SE (1); BE (1); ES (4); FR (5); US (26); GB (7)