Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas
6 Months
24 Years
Both
Leukemia, Lymphoma
Trial Information
Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
assessment of efficacy, safety, pharmacokinetics, immunogenicity.
Outcome Time Frame:
end of study
Safety Issue:
Yes
Principal Investigator
Alan S. Wayne, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000352020
NCT ID:
NCT00077493
Start Date:
January 2004
Completion Date:
October 2008
Related Keywords:
- Leukemia
- Lymphoma
- recurrent childhood acute lymphoblastic leukemia
- Burkitt lymphoma
- recurrent childhood large cell lymphoma
- recurrent childhood lymphoblastic lymphoma
- childhood non-Hodgkin lymphoma
- Leukemia
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma
- Lymphoma, Non-Hodgkin
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda, Maryland 20892-1182 |
