LMB-2 Immunotoxin in Treating Young Patients With Relapsed or Refractory Leukemia or Lymphoma

April 29, 2015 updated by: National Cancer Institute (NCI)

Pediatric Phase I Trial of LMB-2 for Refractory CD25-Positive Leukemias and Lymphomas

RATIONALE: LMB-2 immunotoxin can locate cancer cells and kill them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of LMB-2 immunotoxin in treating young patients with relapsed or refractory leukemia or lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of LMB-2 immunotoxin in pediatric patients with CD-25 positive relapsed or refractory leukemia or lymphoma.
  • Determine the toxic effects of this drug in these patients.
  • Determine the pharmacokinetics of this drug, including the terminal elimination serum half-life, area under the curve, volume of distribution, and relationship to disease burden, in these patients.

Secondary

  • Evaluate the immonogenicity of this drug in these patients.
  • Determine response in patients treated with this drug.
  • Determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression, neutralizing antibodies (i.e., > 75% of the activity of 1 µg/mL of LMB-2 immunotoxin), or unacceptable toxicity. Patients achieving complete remission (CR) receive 2 additional courses beyond CR. Patients with acute lymphoblastic leukemia also receive cytarabine and hydrocortisone intrathecally once monthly concurrent with restaging lumbar punctures.

Cohorts of 3-6 patients receive escalating doses of LMB-2 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, a total of 12 patients are treated at that dose level.

Patients are followed weekly for 1 month and then monthly thereafter.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 2-4 years.

Study Type

Interventional

Enrollment (Anticipated)

40

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
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory University
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Doernbecher Children's Hospital at Oregon Health & Science University
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

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

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Non-Hodgkin's lymphoma, including the following subtypes:

      • Lymphoblastic lymphoma
      • Burkitt's lymphoma
      • Large cell lymphoma
      • Adult T-cell leukemia/lymphoma
      • Cutaneous T-cell lymphoma
      • Peripheral T-cell lymphoma
    • Hodgkin's disease
    • Acute myeloid leukemia
    • Chronic myelogenous leukemia

    • Acute lymphoblastic leukemia (ALL)

      • More than 5% blasts in the bone marrow (i.e., M2 marrow classification)

    • Acute hybrid leukemia, including the following subtypes:

      • Mixed lineage leukemia
      • Biphenotypic leukemia
      • Undifferentiated leukemia

  • CD25-positive (CD25+) disease, meeting 1 of the following criteria:

    • More than 15% of malignant cells are CD25+ by immunohistochemistry with anti-CD25 antibody
    • More than 30% of malignant cells from a site are CD25+ by fluorescence-activated cell sorting analysis
  • Measurable or evaluable disease
  • Relapsed or refractory disease after at least 1 standard chemotherapy regimen AND 1 salvage regimen
  • No available alternative curative therapies
  • Ineligible for or refused hematopoietic stem cell transplantation OR disease activity that prohibits the required time to identify a suitable stem cell donor

  • No CNS leukemia or lymphoma, as evidenced by any of the following criteria:

    • Cerebrospinal fluid (CSF) WBC > 5/µl AND confirmation of CSF blasts
    • Cranial neuropathies secondary to underlying malignancy

    • CNS lymphoma detected by radiological imaging

      • Prior CNS involvement with no current evidence of CNS malignancy allowed
  • No isolated testicular ALL

PATIENT CHARACTERISTICS:

Age

  • 6 months to 21 years

Performance status

  • ECOG 0-3 (≥ 12 years of age)
  • Lansky 40-100% (< 12 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Pancytopenia due to disease allowed

  • For patients without bone marrow involvement:

    • Absolute neutrophil count > 1,000/mm^3
    • Platelet count > 50,000/mm^3 (transfusion independent)

Hepatic

  • Bilirubin ≤ 2.0 mg/dL
  • AST and ALT ≤ 5 times upper limit of normal
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative

Renal

  • Creatinine clearance ≥ 60 mL/min OR

  • Creatinine, meeting the following age-related criteria:

    • ≤ 0.8 mg/dL (≤ 5 years of age)
    • ≤ 1.0 mg/dL (6 to 10 years of age)
    • ≤ 1.2 mg/dL (11 to 15 years of age)
    • ≤ 1.5 mg/dL (> 15 years of age)
  • Calcium 2.0-2.9 mmol/L

Cardiovascular

  • Ejection fraction ≥ 45% by MUGA OR
  • Shortening fraction ≥ 28% by echocardiogram

Pulmonary

  • Oxygen saturation ≥ 90%

Other

  • Sodium 130-150 mmol/L
  • Potassium 3.0-5.5 mmol/L
  • Magnesium 0.5-1.23 mmol/L
  • HIV negative
  • 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 conditions that would preclude study compliance
  • No serum that neutralizes > 75% of the activity of 1 μg/mL of LMB-2 immunotoxin in tissue culture (due to either anti-toxin or anti-mouse immunoglobulin G antibodies)
  • No active graft-vs-host disease (i.e., off immunosuppression)

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior autologous bone marrow transplantation (BMT) allowed
  • At least 100 days since prior allogeneic BMT
  • At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)

Chemotherapy

  • At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) except intrathecal chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Concurrent corticosteroids allowed provided the dose has been stable for the past week and does not increase during study treatment

    • Tapering or discontinuation of steroids allowed

Radiotherapy

  • At least 3 weeks since prior radiotherapy unless < 10% of marrow is irradiated and measurable disease exists outside the radiation port

Surgery

  • Not specified

Other

  • Recovered from all prior therapy
  • At least 30 days since prior investigational agents
  • Concurrent oral supplementation to maintain normal electrolyte levels allowed
  • No concurrent anticoagulation therapy for disease-related conditions
  • 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)

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

April 1, 2004

Study Registration Dates

First Submitted

June 10, 2004

First Submitted That Met QC Criteria

June 10, 2004

First Posted (Estimate)

June 11, 2004

Study Record Updates

Last Update Posted (Estimate)

April 30, 2015

Last Update Submitted That Met QC Criteria

April 29, 2015

Last Verified

February 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000367333
  • NCI-04-C-0168
  • NCI-5903

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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