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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03384654
Other study ID # CR108432
Secondary ID 2017-003377-3454
Status Completed
Phase Phase 2
First received
Last updated
Start date May 14, 2018
Est. completion date September 27, 2022

Study information

Verified date December 2023
Source Janssen Research & Development, LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 47
Est. completion date September 27, 2022
Est. primary completion date September 22, 2022
Accepts healthy volunteers No
Gender All
Age group 1 Year to 30 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
Daratumumab
Participant will receive daratumumab 16 milligram per kilogram (mg/kg) in cohort 1 and cohort 2.
Vincristine
Participant will receive vincristine 1.5 milligram per meter square (mg/m^2) in cohort 1 and cohort 2.
Prednisone
Participant will receive prednisone 40 mg/m^2 in cohort 1 and cohort 2.
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.
Cytarabine
Participant will receive cytarabine 75 mg/m^2 in cohort 2.
6-mercaptopurine
Participant will receive 6-mercaptopurine 60 mg/m^2 orally daily in cohort 2.
Methotrexate
Participant will receive methotrexate 5 g/m^2 intravenously (IV) in cohort 2.

Locations

Country Name City State
Belgium Universitair Ziekenhuis Gent - UZ GENT Gent
France CHU de Bordeaux, Hopital des Enfants Bordeaux
France IHOPE - Hospices civils de Lyon Lyon
France Hôpital Robert Debré Paris
France Hopital trousseau- APHP Paris
France Hôpital D'Enfants Vandoeuvre les Nancy
Germany Charite-Universitätsmedizin Berlin - Berlin Berlin
Germany Medizinische Hochschule Hannover Hannover
Germany Universitätsklinikum Münster Münster
Israel Schneider Children's Medical Center Petach Tiquva
Italy 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
Netherlands Princess Maxima Center Utrecht
Spain 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
Sweden Karolinska University Hospital Stockholm
United Kingdom Bristol Royal Hospital for Children Bristol
United Kingdom Royal Hospital for Sick Children Glasgow
United Kingdom Leeds Children's Hospital Leeds
United Kingdom Great Ormond Street Hospital London
United Kingdom University College London Hospitals London
United Kingdom Royal Manchester Children's Hospital Manchester
United Kingdom Royal Marsden Hospital Surrey
United States C.S. Mott Children's Hospital Ann Arbor Michigan
United States Children'S Healthcare Of Atlanta/Emory Univ. Dept. Of Pediatrics Atlanta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Dell Children's Medical Center of Central Texas/Children's Blood and Cancer Center Austin Texas
United States Johns Hopkins University Baltimore Maryland
United States University of Alabama at Birmingham Birmingham Alabama
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Nationwide Children's Hospital Columbus Ohio
United States UT Southwestern Medical Center Dallas Texas
United States Connecticut Children's Medical Center Hartford Connecticut
United States Baylor College of Medicine Houston Texas
United States Riley Hospital for Children Indianapolis Indiana
United States Medical College Of Wisconsin Milwaukee Wisconsin
United States Memorial Sloan Kettering Cancer Center New York New York
United States New York University Langone Medical Center New York New York
United States Newark Beth Israel Medical Center Newark New Jersey
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 of Philadelphia Philadelphia Pennsylvania
United States Phoenix Children's Hospital Phoenix Arizona
United States Washington Univeristy School of Medicine/ Pediatrics Saint Louis Missouri
United States University of Utah Primary Children's Medical Center Salt Lake City Utah
United States Stony Brook University Medical Center Stony Brook New York

Sponsors (1)

Lead Sponsor Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary 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)
Primary 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 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary Number of Participants With Anti-daratumumab Antibodies Number of participants with anti-daratumumab antibodies was reported. Up to 4 years 4 months
Secondary 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
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