Immunotoxin in Treating Patients With Leukemia or Lymphoma

April 28, 2015 updated by: National Cancer Institute (NCI)

PHASE I STUDY OF ANTI-TAC(Fv)-PE38 (LMB-2), A RECOMBINANT SINGLE-CHAIN IMMUNOTOXIN FOR TREATMENT OF TAC-EXPRESSING MALIGNANCIES

RATIONALE: Immunotoxins can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of LMB-2 immunotoxin in treating patients who have leukemia or lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Assess the therapeutic efficacy and toxicity of the recombinant immunotoxin LMB-2, an anti-Tac murine monoclonal antibody fragment conjugated to a truncated portion of Pseudomonas exotoxin, in patients with Tac-expressing leukemias and lymphomas.
  • Define the pharmacokinetics of LMB-2, including the terminal elimination serum half-life, area under the curve, and volume of distribution.
  • Evaluate, in a preliminary manner, the immunogenicity of LMB-2 in these patients.
  • Determine the effect of LMB-2 on various components of the circulating cellular immune system.

OUTLINE: This is a dose escalation study.

Patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 15-21 days for up to 10 courses in the absence of disease progression, neutralizing antibodies, or unacceptable toxicity.

Cohorts of 3-6 patients each receive escalating doses of LMB-2 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 patient experiences dose limiting toxicity.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study.

Study Type

Interventional

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
        • Medicine Branch
      • Bethesda, Maryland, United States, 20892
        • Laboratory of Molecular Biology

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed Hodgkin's disease, non-Hodgkin's lymphoma, or leukemia in one of the following categories:

    • Adult T-cell leukemia or lymphoma (ATL)

      • No smoldering ATL
      • No limitation on prior therapy

    • Cutaneous T-cell lymphoma (CTCL)

      • Stages IB-III and failed at least 1 standard therapy
      • Stage IV regardless of prior therapy

    • Stages I-IV peripheral T-cell lymphoma

      • Relapsed after standard chemotherapy
      • Ineligible for or refused salvage chemotherapy or bone marrow transplantation (BMT)

    • B-cell non-Hodgkin's lymphoma (NHL) of any histology

      • Indolent stages II-IV NHL

        • Failed at least 1 standard therapy
        • Disease symptomatic and requiring treatment

      • Aggressive NHL

        • Relapsed after standard chemotherapy
        • Ineligible for or refused salvage chemotherapy or BMT

    • Chronic lymphocytic leukemia (CLL)

      • Rai stages III and IV or Binet stage C
      • Failed standard therapy and at least 1 salvage chemotherapy

    • Primary B-cell prolymphocytic leukemia or prolymphocytic transformation of CLL

      • Failed standard therapy and at least 1 salvage chemotherapy

    • Hairy cell leukemia

      • Failed standard and salvage chemotherapy
      • Ineligible for or refused further salvage chemotherapy or BMT

    • Acute myelogenous leukemia

      • Failed standard chemotherapy
      • Ineligible for or refused salvage chemotherapy or BMT

    • Stages II-IV Hodgkin's disease

      • Failed standard chemotherapy
      • Ineligible for curative salvage radiotherapy or chemotherapy
      • Ineligible for or refused BMT
    • Patients with leukemias or lymphomas not easily classified in above categories who have failed standard therapy and are ineligible for or have refused bone marrow transplant

  • Evidence of interleukin-2 receptor-alpha (IL2Ra) expression by one of the following:

    • Greater than 10% of malignant cells reactive with anti-Tac by immunohistochemistry
    • Greater than 10% of malignant cells from a particular site positive by FACS
    • Greater than 400 IL2Ra sites per malignant cell by radiolabeled anti-Tac binding
    • Soluble IL2Ra level greater than 1,000 U/mL (normal geometric mean 235, with 95% confidence levels of 112-502 U)
    • Hodgkin's disease with measurable disease not amenable to biopsy

  • No CNS disease requiring treatment

    • Malignant cells in CSF allowed if judged not to represent clinically significant leukemic or lymphomatous meningitis (as in CSF contamination by blood)

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 50-100%

Life expectancy:

  • Greater than 2 months

Hematopoietic:

  • Absolute neutrophil count greater than 1,000/mm3*
  • Platelet count greater than 50,000/mm3* NOTE: *nonleukemic patients

Hepatic:

  • AST and ALT less than 5 times normal

Renal:

  • Creatinine less than 2.0 mg/dL OR
  • Creatinine clearance greater than 50 mL/min

Pulmonary:

  • FEV1, TLC, and DLCO greater than 50% of predicted if pulmonary or mediastinal involvement with tumor greater than one third of total thoracic diameter

Other:

  • HIV negative
  • Not pregnant
  • Fertile patients must use effective contraception
  • Serum must neutralize no more than 75% LMB-2 in tissue culture

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • At least 3 weeks since prior interferon

Chemotherapy:

  • See Disease Characteristics
  • At least 3 weeks since prior cytotoxic chemotherapy
  • At least 3 weeks since prior retinoids
  • No concurrent chemotherapy

Endocrine therapy:

  • No concurrent corticosteroids unless begun at least 3 weeks prior to entry and dose not increased during 3 weeks prior to entry

Radiotherapy:

  • See Disease Characteristics
  • At least 3 weeks since prior whole-body electron beam radiotherapy
  • Other radiotherapy allowed within 3 weeks of entry provided less than 10% of marrow irradiated and measurable disease exists outside radiation port

Surgery:

  • Not specified

Other:

  • See Disease Characteristics
  • At least 3 weeks since any prior systemic therapy
  • No other concurrent investigational agents

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

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

April 1, 1996

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

May 5, 2003

First Posted (Estimate)

May 6, 2003

Study Record Updates

Last Update Posted (Estimate)

April 29, 2015

Last Update Submitted That Met QC Criteria

April 28, 2015

Last Verified

March 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000064729
  • NCI-96-C-0064F
  • NCI-T95-0042N

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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