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

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ClinicalTrials.gov Identifier: NCT00389506
Recruitment Status : Withdrawn
First Posted : October 19, 2006
Last Update Posted : March 16, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE October 18, 2006
First Posted Date  ICMJE October 19, 2006
Last Update Posted Date March 16, 2012
Study Start Date  ICMJE September 2006
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: November 8, 2006)
Feasibility of using fludarabine phosphate and cyclophosphamide to decrease neutralizing antibodies
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2006)
  • 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
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 Fludarabine and Cyclophosphamide Followed By LMB-2 Immunotoxin in Treating Patients With Hodgkin's Lymphoma
Official Title  ICMJE A Pilot Study of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Hodgkin's Disease After Fludarabine and Cyclophosphamide
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Biological: LMB-2 immunotoxin
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Other: pharmacological study
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   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 Withdrawn
Actual Enrollment  ICMJE
 (submitted: March 14, 2012)
0
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE May 2008
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
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 NCT00389506
Other Study ID Numbers  ICMJE 060240
06-C-0240
NCI-P6761
NCI-7835
CDR0000508789
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 Institutes of Health Clinical Center (CC)
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Robert Kreitman, MD National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 2012

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