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

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00544570

Purpose

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.

Condition	Intervention
Lymphoma	Drug: carmustine Drug: cyclophosphamide Drug: etoposide Drug: filgrastim Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: radiation therapy Procedure: total-body irradiation

MedlinePlus related topics: Hodgkin's Disease Lymphoma

Drug Information available for: Cyclophosphamide Filgrastim Etoposide Carmustine Melphalan Etoposide phosphate Melphalan hydrochloride Sarcolysin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	High Dose Sequential Therapy for Poor Risk Recurrent or Refractory Hodgkin's Disease

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

Primary Outcome Measures:

Feasibility [ Designated as safety issue: No ]
Toxicity as assessed by NCI CTC v2.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response rate [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Percentage of patients who achieve minimal disease status after 2 courses [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	April 1998

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.

Eligibility

Ages Eligible for Study:	up to 64 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed Hodgkin lymphoma
- Diagnosis reviewed by the participating institution
Failed to achieve complete remission (CR) after first-line chemotherapy or chemoradiotherapy (i.e., induction failure) OR not felt to be curable by radiotherapy alone
Relapsed after standard chemotherapy regimen for Hodgkin lymphoma AND has ≥ 1 of the following poor-risk features:
- Extranodal disease at relapse
- Interval from first CR to relapse < 12 months
- B symptoms at relapse
- Chemo-resistant relapse OR failure to achieve a second CR with conventional nontransplantation salvage chemotherapy regimen
No cytogenetic abnormality on cytogenetic analysis of bone marrow

PATIENT CHARACTERISTICS:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00544570

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Eileen P. Smith, MD

Beckman Research Institute

More Information

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

Study ID Numbers:	CDR0000567466, CHNMC-97160
Study First Received:	October 13, 2007
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00544570
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma

Study placed in the following topic categories:

Melphalan
Immunoproliferative Disorders
Hodgkin's disease
Hodgkin lymphoma, adult
Carmustine
Cyclophosphamide
Etoposide phosphate

Recurrence
Lymphatic Diseases
Hodgkin lymphoma, childhood
Lymphoproliferative Disorders
Lymphoma
Hodgkin Disease
Etoposide

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
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 14, 2009