Phase 2
N=46
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
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT03384654 ↗Enrolled (actual)
46
Serious AEs
65.2%
Results posted
Oct 2023
Primary outcome: Primary: Cohort 1: Percentage of Participants With Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL) — 0 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Daratumumab (Drug); Vincristine (Drug); Prednisone (Drug); Doxorubicin (Drug); Peg-asparaginase (Biological); Cyclophosphamide (Drug); Cytarabine (Drug); 6-mercaptopurine (Drug); Methotrexate (Drug)
- Age
- Pediatric, Adult · 1+ yrs
- Sex
- All
- Sponsor
- Janssen Research & Development, LLC
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cohort 1: Percentage of Participants With Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL) |
— | — |
| PRIMARY Cohort 2: Percentage of Participants With Complete Response (CR) for T-cell ALL |
41.7; 60.0; 30.0 | — |
| SECONDARY Overall Response Rate (ORR) |
14.3; 83.3; 80.0; 50.0 | — |
| SECONDARY Event-free Survival (EFS) |
1.1; 8.9; 10.3; 2.9 | — |
| SECONDARY Relapse-free Survival (RFS) |
19.4; 9.4; NA | — |
| SECONDARY Overall Survival (OS) |
3.2; 10.9; 12.0; 4.2 | — |
| SECONDARY Minimal Residual Disease (MRD) Negative Rate |
0; 45.8; 20.0; 50.0 | — |
| SECONDARY Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) |
14.3; 75.0; 60.0; 30.0 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) of Daratumumab |
494; 763; 501; 758 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) of Daratumumab |
172; 369; 172; 365 | — |
| SECONDARY Number of Participants With Anti-daratumumab Antibodies |
0; 0; 0; 0 | — |
| SECONDARY Concentration of Daratumumab in Cerebrospinal Fluid (CSF) |
NA; NA; NA; NA; 0.907; 0.319 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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 ( =) 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 =) 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)
- 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
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:
- 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)
Data sourced from ClinicalTrials.gov (NCT03384654). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.