BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
RATIONALE: BL22 immunotoxin can locate tumor cells and kill them without harming normal cells. BL22 immunotoxin may be effective in treating relapsed or refractory acute lymphoblastic leukemia and non-Hodgkin's lymphoma.
PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating young patients with relapsed or refractory acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
|Leukemia Lymphoma||Drug: BL22 immunotoxin Procedure: antibody-drug conjugate therapy Procedure: immunotoxin therapy Procedure: monoclonal antibody therapy||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas|
- assessment of efficacy, safety, pharmacokinetics, immunogenicity. [ Time Frame: end of study ]
- Expansion of MTD [ Time Frame: end of study ]
|Study Start Date:||January 2004|
|Estimated Study Completion Date:||October 2008|
|Estimated Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Drug: BL22 immunotoxin
BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses.
Active Comparator: 2
Procedure: antibody-drug conjugate therapy
CD22 antibody, RFB4 on day 7
Active Comparator: 3
Procedure: immunotoxin therapy
tested for immunogenicity to CAT-8015 before each cycle and at end of study.
Active Comparator: 4
monoclonal antibody therapy
Procedure: monoclonal antibody therapy
administered intravenously over 30 minutes.
- Determine the toxic effects of BL22 immunotoxin in pediatric patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
- Determine the maximum tolerated dose of this drug in these patients.
- Determine the immunogenicity of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the in vitro cytotoxicity of this drug against lymphoblasts from patients with acute lymphoblastic leukemia.
- Determine the therapeutic efficacy of this drug in inducing remissions in these patients.
- Determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug.
OUTLINE: This is a non-randomized, dose-escalation study.
Patients receive BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses.
Cohorts of 3-6 patients receive escalating doses of BL22 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, the cohort is expanded and a total of 12 patients are treated at that dose.
Patients are followed weekly for at least 1 month and then every 1-3 months thereafter.
PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00077493
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|Principal Investigator:||Alan S. Wayne, MD||National Cancer Institute (NCI)|