BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma

Sponsor

MedImmune LLC (Industry)

Overall Status

Suspended

CT.gov ID

NCT00077493

Collaborator

Cambridge Antibody Technology (Other)

Enrollment

Location

Arms

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma	Drug: BL22 immunotoxin Procedure: antibody-drug conjugate therapy Procedure: immunotoxin therapy Procedure: monoclonal antibody therapy	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

95 participants

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

Study Start Date :

Jan 1, 2004

Anticipated Primary Completion Date :

Oct 1, 2008

Anticipated Study Completion Date :

Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

assessment of efficacy, safety, pharmacokinetics, immunogenicity. [end of study]

Secondary Outcome Measures

Expansion of MTD [end of study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 24 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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