Fludarabine and Cyclophosphamide Followed By LMB-2 Immunotoxin in Treating Patients With Hodgkin's Lymphoma

March 14, 2012 updated by: National Institutes of Health Clinical Center (CC)

A Pilot Study of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Hodgkin's Disease After Fludarabine and Cyclophosphamide

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. LMB-2 immunotoxin can find cancer cells and kill them without harming normal cells. Giving fludarabine and cyclophosphamide followed by LMB-2 immunotoxin may kill more cancer cells.

PURPOSE: This clinical trial is studying how well giving fludarabine and cyclophosphamide followed by LMB-2 immunotoxin works in treating patients with Hodgkin's lymphoma.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the feasibility of pretreatment with fludarabine phosphate and cyclophosphamide in preventing neutralization of antibodies in patients with CD25-positive Hodgkin's lymphoma.

Secondary

  • Determine the response rate in patients treated with LMB-2 immunotoxin.
  • Determine the response duration in patients receiving this treatment.
  • Correlate serum levels of LMB-2 immunotoxin with toxicity and response in these patients.
  • Assess the development of neutralizing antibodies and the effect of these antibodies on blood levels of LMB-2 immunotoxin and toxicity.
  • Correlate soluble Tac-peptide levels with treatment response in these patients.

OUTLINE: This is a nonrandomized, pilot study.

Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-4 and filgrastim (G-CSF) subcutaneously once daily beginning on day 5 and continuing until blood counts recover.

Beginning 4 weeks after completion of chemotherapy, 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.

Blood is obtained prior to and after chemotherapy and then periodically during LMB-2 immunotoxin therapy for pharmacokinetic studies to measure lymphocyte subsets.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Type

Interventional

Phase

  • Not Applicable

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histopathologically confirmed CD25+ Hodgkin's lymphoma

    • At least 20% of the malignant cells positive by immunohistochemistry
    • Stage II-IV disease

  • Meets the following criteria:

    • Failed standard chemotherapy
    • Not eligible for curative salvage radiotherapy or chemotherapy
    • Not eligible for or refused bone marrow transplantation
  • Measurable disease
  • No patient whose serum neutralizes LMB-2 immunotoxin in tissue culture, due either to antitoxin or antimouse-IgG antibodies
  • No patient whose serum neutralizes > 75% of the activity of 1 µg/mL of LMB-2 immunotoxin

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 50,000/mm³
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • ALT and AST ≤ 2.5 times upper limit of normal
  • Albumin ≥ 3.0 g/dL
  • Bilirubin ≤ 2.2 mg/dL (< 5 mg/dL if Gilbert's syndrome is present)
  • Creatinine ≤ 1.4 mg/dL OR creatinine clearance ≥ 50 mL/min

  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situations that would limit study compliance

  • No HIV or hepatitis C positivity

    • Hepatitis B surface antigen positivity allowed provided patient is receiving lamivudine
  • LVEF ≥ 45%
  • DLCO ≥ 50% of normal OR FEV_1 ≥ 60% of normal
  • No active second malignancy requiring treatment

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No systemic cytotoxic chemotherapy within the past 4 weeks
  • No systemic steroids (except stable doses of prednisone ≤ 20 mg/day) within the past 4 weeks
  • No monoclonal antibody therapy within the past 12 weeks
  • No prior LMB-2 immunotoxin
  • No concurrent warfarin

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Feasibility of using fludarabine phosphate and cyclophosphamide to decrease neutralizing antibodies

Secondary Outcome Measures

Outcome Measure
Response rate
Response duration
Correlation of serum levels of LMB-2 immunotoxin with toxicity and response
Development of neutralizing antibodies and its effect on blood level of LMB-2 immunotoxin and toxicity
Correlation of soluble Tac-peptide with treatment response

Collaborators and Investigators

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

Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

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

September 1, 2006

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

October 18, 2006

First Submitted That Met QC Criteria

October 18, 2006

First Posted (Estimate)

October 19, 2006

Study Record Updates

Last Update Posted (Estimate)

March 16, 2012

Last Update Submitted That Met QC Criteria

March 14, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 060240
  • 06-C-0240
  • NCI-P6761
  • NCI-7835
  • CDR0000508789

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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