Precursor Cell Lymphoblastic Leukemia-Lymphoma Clinical Trial
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
Verified date | December 2023 |
Source | Janssen Research & Development, LLC |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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) |
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 |
Lead Sponsor | Collaborator |
---|---|
Janssen Research & Development, LLC |
United States, Belgium, France, Germany, Israel, Italy, Netherlands, Spain, Sweden, United Kingdom,
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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