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

Lymphoma Clinical Trial

Official title:

Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00077493
• Other study ID #: CDR0000352020
• Secondary ID: NCI-04-C-0079HNC
• Status: Suspended
• Phase: Phase 1
• First received: February 10, 2004
• Last updated: December 21, 2007
• Start date: January 2004
• Est. completion date: October 2008

Study information

• Verified date: December 2007
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00075309

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 95
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 24 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Procedure:
• antibody-drug conjugate therapy
CD22 antibody, RFB4 on day 7
• immunotoxin therapy
tested for immunogenicity to CAT-8015 before each cycle and at end of study.
• monoclonal antibody therapy
administered intravenously over 30 minutes.

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
MedImmune LLC	Cambridge Antibody Technology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	assessment of efficacy, safety, pharmacokinetics, immunogenicity.		end of study	Yes
Secondary	Expansion of MTD		end of study	Yes