BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia Lymphoma |
Drug: BL22 immunotoxin Procedure: antibody-drug conjugate therapy Procedure: immunotoxin therapy Procedure: monoclonal antibody therapy |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: 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 ] [ Designated as safety issue: Yes ]
- Expansion of MTD [ Time Frame: end of study ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 95 |
| 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) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
BL22 immunotoxin
|
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
antibody therapy
|
Procedure: antibody-drug conjugate therapy
CD22 antibody, RFB4 on day 7
|
|
Active Comparator: 3
immunotoxin therapy
|
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.
|
Detailed Description:
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Eligibility| Ages Eligible for Study: | 6 Months to 24 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (including lymphoblastic lymphoma, Burkitt's lymphoma, and large cell lymphoma)
- Not amenable to available curative therapies
- Relapsed or refractory disease after at least 1 standard chemotherapy and 1 salvage regimen
CD22 positive according to at least 1 of the following criteria:
- More than 15% CD22-positive malignant cells by immunohistochemistry
- More than 30% CD22-positive malignant cells by fluorescent-activated cell sorter analysis
- Measurable or evaluable disease
- Prior CNS involvement allowed provided there is no current evidence of CNS malignancy
No CNS leukemia or lymphoma as manifested by any of the following:
- Cerebrospinal fluid (CSF) WBC ≥ 5/mm^3 and confirmation of CSF blasts
- Cranial neuropathies secondary to underlying malignancy
- Radiologically detected CNS lymphoma
- No isolated testicular ALL
- Ineligible for or refused hematopoietic stem cell transplantation OR has disease activity that prohibits the time required to identify a suitable stem cell donor
PATIENT CHARACTERISTICS:
Age
- 6 months to 24 years
Performance status
- ECOG 0-3 (12 to 24 years of age)
- Lansky 40-100% (under 12 years of age)
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
- Absolute neutrophil count > 1,000/mm^3 *
- Platelet count > 50,000/mm^3 * NOTE: *Non-leukemic patients only
Hepatic
- Bilirubin ≤ 2.0 mg/dL
- AST and ALT ≤ 5 times upper limit of normal
- No active hepatitis B or C infection
Renal
- Creatinine normal for age OR
- Creatinine clearance ≥ 60 mL/min
Immunologic
- No serum neutralization of more than 75% of the activity of 1 µg/mL of study drug
- HIV negative
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No clinically significant unrelated systemic illness that would preclude study participation
- No other significant organ dysfunction that would preclude study participation
- No psychiatric illness or social situation that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
- Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) allowed
- More than 100 days since prior allogeneic HSCT
Chemotherapy
- See Disease Characteristics
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas)
Endocrine therapy
Concurrent corticosteroids allowed provided there has been no increase in the dose 1 week prior to and after study entry
- Steroid taper allowed
Radiotherapy
At least 3 weeks since prior radiotherapy
- Allowed in the past 3 weeks provided the volume of the bone marrow treated is < 10% AND the patients has measurable disease outside of the radiation port
Surgery
- Not specified
Other
- Recovered from prior therapy
- At least 30 days since prior investigational drugs
- No other concurrent investigational drugs
Contacts and Locations| 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) |
More Information
No publications provided
| Responsible Party: | Karen Kaucic, M.D., MedImmune Inc. |
| ClinicalTrials.gov Identifier: | NCT00077493 History of Changes |
| Obsolete Identifiers: | NCT00075309 |
| Other Study ID Numbers: | CDR0000352020, NCI-04-C-0079H, NCI-5643 |
| Study First Received: | February 10, 2004 |
| Last Updated: | December 21, 2007 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by MedImmune LLC:
|
recurrent childhood acute lymphoblastic leukemia Burkitt lymphoma recurrent childhood large cell lymphoma recurrent childhood lymphoblastic lymphoma childhood non-Hodgkin lymphoma |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphoma Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases |
Immunoproliferative Disorders Immune System Diseases Antibodies Immunoglobulins Antibodies, Monoclonal Immunotoxins Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013