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

Primary Purpose

Lymphoma

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

LMB-2 immunotoxin

cyclophosphamide

fludarabine phosphate

pharmacological study

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Outcomes

Primary Outcome Measures

Feasibility of using fludarabine phosphate and cyclophosphamide to decrease neutralizing antibodies

Secondary Outcome Measures

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

Full Information

NCT ID

NCT00389506

First Posted

October 18, 2006

Last Updated

March 14, 2012

Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00389506

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

March 2012

Overall Recruitment Status

Withdrawn

Study Start Date

September 2006 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

May 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

LMB-2 immunotoxin

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Intervention Type

Drug

Intervention Name(s)

fludarabine phosphate

Intervention Type

Other

Intervention Name(s)

pharmacological study

Primary Outcome Measure Information:

Title

Feasibility of using fludarabine phosphate and cyclophosphamide to decrease neutralizing antibodies

Secondary Outcome Measure Information:

Title

Response rate

Title

Response duration

Title

Correlation of serum levels of LMB-2 immunotoxin with toxicity and response

Title

Development of neutralizing antibodies and its effect on blood level of LMB-2 immunotoxin and toxicity

Title

Correlation of soluble Tac-peptide with treatment response

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert Kreitman, MD

Organizational Affiliation

National Cancer Institute (NCI)

Official's Role

Study Chair

Facility Information:

Facility Name

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892-1182

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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