Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Biomarker/Laboratory analysis, Treatment Completed 18 and over NCI NCI-06-C-0240 NCI-P6761, 7835, NCI-7835, NCT00389506

Objectives

Primary

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

Secondary

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

Entry Criteria

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

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

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 FEV₁ ≥ 60% of normal
• No active second malignancy requiring treatment

Expected Enrollment

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

Outcomes

Feasibility of using fludarabine phosphate and cyclophosphamide to decrease neutralizing antibodies

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

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Robert Kreitman, MD, Protocol chair		Ph: 301-496-6947 Email: kreitmar@mail.nih.gov

Related Information

Web site for additional information

Registry Information
Official Title		A Pilot Study of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Hodgkin's Disease after Fludarabine and Cyclophosphamide
Trial Start Date		2006-09-05
Trial Completion Date		2008-05-16
Registered in ClinicalTrials.gov		NCT00389506
Date Submitted to PDQ		2006-09-06
Information Last Verified		2008-05-20