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

NCT ID: NCT00077493

Last Updated: 2007-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE1

Total Enrollment

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-01-31

Study Completion Date

2008-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leukemia Lymphoma

Keywords

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recurrent childhood acute lymphoblastic leukemia Burkitt lymphoma recurrent childhood large cell lymphoma recurrent childhood lymphoblastic lymphoma childhood non-Hodgkin lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

BL22 immunotoxin

Group Type ACTIVE_COMPARATOR

BL22 immunotoxin

Intervention Type DRUG

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.

2

antibody therapy

Group Type ACTIVE_COMPARATOR

antibody-drug conjugate therapy

Intervention Type PROCEDURE

CD22 antibody, RFB4 on day 7

3

immunotoxin therapy

Group Type ACTIVE_COMPARATOR

immunotoxin therapy

Intervention Type PROCEDURE

tested for immunogenicity to CAT-8015 before each cycle and at end of study.

4

monoclonal antibody therapy

Group Type ACTIVE_COMPARATOR

monoclonal antibody therapy

Intervention Type PROCEDURE

administered intravenously over 30 minutes.

Interventions

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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.

Intervention Type DRUG

antibody-drug conjugate therapy

CD22 antibody, RFB4 on day 7

Intervention Type PROCEDURE

immunotoxin therapy

tested for immunogenicity to CAT-8015 before each cycle and at end of study.

Intervention Type PROCEDURE

monoclonal antibody therapy

administered intravenously over 30 minutes.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

6 Months

Maximum Eligible Age

24 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cambridge Antibody Technology

OTHER

Sponsor Role collaborator

MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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MedImmune Inc.

Principal Investigators

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Alan S. Wayne, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-04-C-0079H

Identifier Type: -

Identifier Source: secondary_id

NCI-5643

Identifier Type: -

Identifier Source: secondary_id

CDR0000352020

Identifier Type: -

Identifier Source: org_study_id

NCT00075309

Identifier Type: -

Identifier Source: nct_alias