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

NCT ID: NCT03384654

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-14
• Study Completion Date: 2022-09-27

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.

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.

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

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

Vincristine

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

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

Vincristine

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Peg-asparaginase

Intervention Type: BIOLOGICAL

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

Cyclophosphamide

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

6-mercaptopurine

Intervention Type: DRUG

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

Methotrexate

Intervention Type: DRUG

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

Interventions

Daratumumab

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

Intervention Type: DRUG

Vincristine

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

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Peg-asparaginase

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

Intervention Type: BIOLOGICAL

Cyclophosphamide

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

Intervention Type: DRUG

Cytarabine

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

Intervention Type: DRUG

6-mercaptopurine

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

Intervention Type: DRUG

Methotrexate

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

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Phoenix Children's Hospital

Phoenix, Arizona, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Children's Hospital Orange County

Orange, California, United States

Stanford University

Palo Alto, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

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

Atlanta, Georgia, United States

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

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Washington Univeristy School of Medicine/ Pediatrics

St Louis, Missouri, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

New York University Langone Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

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

Austin, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah Primary Children's Medical Center

Salt Lake City, Utah, United States

Medical College Of Wisconsin

Milwaukee, Wisconsin, United States

Universitair Ziekenhuis Gent - UZ GENT

Ghent, , Belgium

CHU de Bordeaux, Hopital des Enfants

Bordeaux, , France

IHOPE - Hospices civils de Lyon

Lyon, , France

Hopital trousseau- APHP

Paris, , France

Hôpital Robert Debré

Paris, , France

Hôpital D'Enfants

Vandœuvre-lès-Nancy, , France

Charite-Universitätsmedizin Berlin - Berlin

Berlin, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitatsklinikum Munster

Münster, , Germany

Schneider Children's Medical Center

Petach Tiquva, , Israel

Istituto Giannina Gaslini

Genova, , Italy

Fondazione MBBM, ASST Monza

Monza, , Italy

Ospedale Pediatrico Bambin Gesù

Roma, , Italy

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

Torino, , Italy

Princess Maxima Center

Utrecht, , Netherlands

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Sant Joan de Deu

Esplugues de Llobregat, , Spain

Hosp. Infantil Univ. Nino Jesus

Madrid, , Spain

Hosp. Univ. I Politecni La Fe

Valencia, , Spain

Karolinska University Hospital

Stockholm, , Sweden

Bristol Royal Hospital for Children

Bristol, , United Kingdom

Royal Hospital for Sick Children

Glasgow, , United Kingdom

Leeds Children's Hospital

Leeds, , United Kingdom

University College London Hospitals

London, , United Kingdom

Great Ormond Street Hospital

London, , United Kingdom

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Royal Marsden Hospital

Surrey, , United Kingdom

Countries

United States; Belgium; France; Germany; Israel; Italy; Netherlands; Spain; Sweden; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39158071 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33245179 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-003377-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

54767414ALL2005

Identifier Type: OTHER

Identifier Source: secondary_id

CR108432

Identifier Type: -

Identifier Source: org_study_id