High-Dose Chemotherapy in Treating Patients Undergoing Stem Cell Transplant for Recurrent or Refractory Hodgkin's Lymphoma

NCT ID: NCT00544570

Last Updated: 2010-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-04-30
• Study Completion Date: 2007-12-31

Brief Summary

RATIONALE: Giving high-dose chemotherapy before a peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or by killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by high-dose chemotherapy and radiation therapy.

PURPOSE: This clinical trial is studying the side effects and how well high-dose chemotherapy works in treating patients undergoing stem cell transplant for recurrent or refractory Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

• To evaluate the feasibility and toxicity of high-dose sequential therapy comprising high-dose etoposide and cyclophosphamide with filgrastim (G-CSF) support followed by 2 courses of high-dose therapy and autologous stem cell transplantation in patients with poor-risk recurrent or refractory Hodgkin lymphoma.
• To analyze the response rate, progression-free survival, and overall survival of patients treated with this regimen.
• To determine the percentage of patients who can achieve a minimal disease status after two courses of Hodgkin lymphoma chemotherapy and before "classical autologous stem cell transplantation."

OUTLINE:

• First high-dose chemotherapy*: Patients receive high-dose cyclophosphamide IV over 2 hours followed by etoposide IV over 4 hours.

NOTE: *Patients with minimal disease (i.e., a single lymph node ≤ 2 cm in maximal horizontal diameter or a > 75% reduction in a bulky (≥ 10 cm) tumor mass AND no morphological evidence of active bone marrow disease) at initial evaluation do not receive the first high-dose chemotherapy but proceed directly to peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF) for 3 days and PBSC collection beginning on day 4.

• Peripheral stem cell mobilization and collection: Patients receive G-CSF subcutaneously beginning 96 hours after completion of etoposide and continuing through completion of PBSC collection. Patients undergo leukapheresis to collect PBSC for reinfusion after additional high-dose therapy.
• Second high-dose chemotherapy: Patients receive high-dose melphalan IV over 30 minutes on day -1.
• First PBSC infusion: At least 24 hours after completion of melphalan, patients undergo reinfusion of PBSC on day 0.
• Local radiotherapy: Patients with a localized tumor mass > 5 cm after the second course of chemotherapy or a previous history of bulky disease (> 10 cm or mediastinal mass > 1/3 of transverse thoracic diameter) that has not been irradiated may receive local radiotherapy for 2 weeks, at the discretion of the principal investigator.
• High-dose therapy: Eight to 12 weeks after completion of the second course of chemotherapy, patients receive 1 of 2 regimens.

• Regimen A: Patients undergo fractionated total body irradiation 3 times daily on days -8 to -5 (10 fractions) and receive high-dose etoposide IV over 4 hours on day -4 and cyclophosphamide IV on day -2.
• Regimen B: Patients receive high-dose carmustine IV over 4 hours on days -7 to -5 and etoposide and cyclophosphamide as in regimen A.
• Second PBSC infusion: At least 48 hours after completion of cyclophosphamide, patients undergo reinfusion of PBSC on day 0.

After completion of study therapy, patients are followed at day 60 and then every 3 months for up to 1 year.

Conditions

Lymphoma

Study Design

• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

total-body irradiation

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• SWOG performance status 0-1
• LVEF > 50% by 2D-ECHO or MUGA scan

• Patients with LVEF between 45-50% and without wall motion abnormalities are assessed on an individual basis after consultation with the cardiologist
• FEV_1 or DLCO > 45% predicted
• Creatinine clearance > 60 mL/min
• HIV-negative
• Hepatitis B surface antigen-negative
• Hepatitis C virus-negative
• ALT ≤ 5 times upper limit of normal
• No inadequate vital organ function
• No active infection
• Fertile patients must use adequate contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent, post-transplantation, consolidative radiotherapy to residual masses allowed provided the patient has engrafted with a WBC > 4,000/μL and a platelet count > 100,000/μL

• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

City of Hope Medical Center

Principal Investigators

Eileen P. Smith, MD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P01CA030206

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-97160

Identifier Type: -

Identifier Source: secondary_id

CDR0000567466

Identifier Type: -

Identifier Source: org_study_id