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

December 21, 2007 updated by: MedImmune LLC

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

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.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

95

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 24 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
assessment of efficacy, safety, pharmacokinetics, immunogenicity.
Time Frame: end of study
end of study

Secondary Outcome Measures

Outcome Measure
Time Frame
Expansion of MTD
Time Frame: end of study
end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MedImmune LLC

Collaborators

Cambridge Antibody Technology

Investigators

  • Principal Investigator: Alan S. Wayne, MD, National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2004

Primary Completion (Anticipated)

October 1, 2008

Study Completion (Anticipated)

October 1, 2008

Study Registration Dates

First Submitted

February 10, 2004

First Submitted That Met QC Criteria

February 11, 2004

First Posted (Estimate)

February 12, 2004

Study Record Updates

Last Update Posted (Estimate)

December 28, 2007

Last Update Submitted That Met QC Criteria

December 21, 2007

Last Verified

December 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000352020
  • NCI-04-C-0079H
  • NCI-5643

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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