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

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• Recruitment Status: Withdrawn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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Biological: LMB-2 immunotoxin; Drug: cyclophosphamide; Drug: fludarabine phosphate; Other: pharmacological study	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Non-Randomized
• Primary Purpose: Treatment
• 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
• Study Start Date: September 2006
• Actual Study Completion Date: May 2008

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Feasibility of using fludarabine phosphate and cyclophosphamide to decrease neutralizing antibodies

Secondary Outcome Measures :

1. Response rate
2. Response duration
3. Correlation of serum levels of LMB-2 immunotoxin with toxicity and response
4. Development of neutralizing antibodies and its effect on blood level of LMB-2 immunotoxin and toxicity
5. Correlation of soluble Tac-peptide with treatment response

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

Contacts and Locations

Locations

United States, Maryland

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Institutes of Health Clinical Center (CC)

National Cancer Institute (NCI)

Investigators

• Study Chair: Robert Kreitman, MD; National Cancer Institute (NCI)

More Information

• ClinicalTrials.gov Identifier: NCT00389506
• Other Study ID Numbers: 060240; 06-C-0240; NCI-P6761; NCI-7835; CDR0000508789
• First Posted: October 19, 2006
• Last Update Posted: March 16, 2012
• Last Verified: March 2012

Keywords provided by National Institutes of Health Clinical Center (CC):

stage II adult Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; recurrent adult Hodgkin lymphoma

Additional relevant MeSH terms:

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Immunotoxins; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antimetabolites, Antineoplastic; Antimetabolites