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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00389506
First received: October 18, 2006
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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 Intervention
Lymphoma
Biological: LMB-2 immunotoxin
Drug: cyclophosphamide
Drug: fludarabine phosphate
Other: pharmacological study

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Feasibility of using fludarabine phosphate and cyclophosphamide to decrease neutralizing antibodies [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Response duration [ Designated as safety issue: No ]
  • Correlation of serum levels of LMB-2 immunotoxin with toxicity and response [ Designated as safety issue: Yes ]
  • Development of neutralizing antibodies and its effect on blood level of LMB-2 immunotoxin and toxicity [ Designated as safety issue: Yes ]
  • Correlation of soluble Tac-peptide with treatment response [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: September 2006
Study Completion Date: May 2008
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389506

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Robert Kreitman, MD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00389506     History of Changes
Other Study ID Numbers: 060240, 06-C-0240, NCI-P6761, NCI-7835, CDR0000508789
Study First Received: October 18, 2006
Last Updated: March 14, 2012
Health Authority: United States: Food and Drug Administration

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:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Immunotoxins
Antibodies, Monoclonal
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 22, 2014