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

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00389506

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	Drug: LMB-2 immunotoxin Drug: cyclophosphamide Drug: fludarabine phosphate Procedure: pharmacological study

MedlinePlus related topics: Cancer Hodgkin's Disease Lymphoma

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Dacliximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
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

Further study details as provided by National Cancer Institute (NCI):

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 ]

Estimated Enrollment:	30
Study Start Date:	September 2006
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

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

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

National Cancer Institute (NCI)

Investigators

Study Chair:

Robert Kreitman, MD

National Cancer Institute (NCI)

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000508789, NCI-06-C-0240, NCI-P6761, NCI-7835
Study First Received:	October 18, 2006
Last Updated:	December 13, 2008
ClinicalTrials.gov Identifier:	NCT00389506
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Immunoproliferative Disorders
Hodgkin's disease
Hodgkin lymphoma, adult
Daclizumab
Cyclophosphamide
Fludarabine monophosphate
Recurrence
Immunotoxins

Antibodies, Monoclonal
Lymphatic Diseases
Antibodies
Fludarabine
Lymphoproliferative Disorders
Lymphoma
Hodgkin Disease
Immunoglobulins

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009