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Immunotoxin in Treating Patients With Leukemia or Lymphoma

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ClinicalTrials.gov Identifier: NCT00002765
Recruitment Status : Completed
First Posted : May 6, 2003
Last Update Posted : April 29, 2015
Sponsor:
Information provided by:
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE May 6, 2003
Last Update Posted Date April 29, 2015
Study Start Date  ICMJE April 1996
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immunotoxin in Treating Patients With Leukemia or Lymphoma
Official Title  ICMJE PHASE I STUDY OF ANTI-TAC(Fv)-PE38 (LMB-2), A RECOMBINANT SINGLE-CHAIN IMMUNOTOXIN FOR TREATMENT OF TAC-EXPRESSING MALIGNANCIES
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
Intervention  ICMJE Biological: LMB-2 immunotoxin
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00002765
Other Study ID Numbers  ICMJE CDR0000064729
NCI-96-C-0064F
NCI-T95-0042N
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Robert Kreitman, MD National Cancer Institute (NCI)
PRS Account National Cancer Institute (NCI)
Verification Date March 2003

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP