Autologous Stem Cell Transplant in Treating Patients With Progressive or Recurrent Hodgkin's Lymphoma

Tandem Autologous Stem Cell Transplantation for Patients With Primary Progressive or Poor Risk Recurrent Hodgkin's Disease

RATIONALE: Giving two autologous stem cell transplants (one after the other) may be an effective treatment for Hodgkin's lymphoma.

PURPOSE: This phase II trial is studying how well giving two autologous stem cell transplants works in treating patients with progressive or recurrent Hodgkin's lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: etoposide; Drug: melphalan; Procedure: autologous-autologous tandem hematopoietic stem cell transplantation; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

Primary

• Determine the 3-year progression-free survival of patients with progressive or recurrent Hodgkin's lymphoma treated with tandem autologous stem cell transplantation (2 courses of high-dose therapy with autologous stem cell rescue).
• Determine the response rate in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a pilot study. Patients are stratified according to risk (poor risk [primary progressive, recurrent, or resistant relapse] vs good risk [first recurrence]).

• Salvage therapy (for patients with relapsed disease after achieving a previous complete response): Patients receive at least 2 courses of salvage chemotherapy or radiotherapy.
• Autologous hematopoietic stem cell collection: Patients undergo autologous hematopoietic stem cell collection. Patients with an inadequate number of collected stem cells are removed from the study.
• First preparative regimen: Patients receive high-dose melphalan IV continuously over 16 hours on day -1.
• First autologous stem cell transplantation (SCT): Patients undergo autologous SCT on day 0. They also receive filgrastim (G-CSF) IV over 30 minutes once daily beginning on day 5 and continuing until blood counts recover. At least 4-8 weeks later, patients proceed to second preparative regimen.
• Second preparative regimen: Patients receive high-dose carmustine IV over 1-2 hours on days -6, -5, and -4, etoposide IV over 4 hours on day -3, and cyclophosphamide IV over 2 hours on day -2. Beginning 36-48 hours later, patients proceed to the second autologous SCT (day 0).
• Second autologous SCT: Patients undergo second autologous SCT on day 0. Patients also receive filgrastim (G-CSF) IV over 30 minutes once daily beginning on day 5 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically* confirmed Hodgkin's lymphoma meeting ≥ 1 of the following criteria:

  • Disease progression during initial first line chemotherapy
  • Complete response lasting ≤ 90 days after induction
  • Partial response lasting ≤ 90 days after induction
  • First recurrence/progression with the duration of initial response ≤ 12 months after completion of chemotherapy NOTE: *There must be unequivocal radiological evidence of recurrent or progressive disease if biopsy was not obtained at time of disease recurrence/progression
• No clonal abnormalities in marrow collection
• Must have bilateral or unilateral bone marrow aspirates and biopsy within 42 days prior to stem cell collection

• Must have adequate sections of original diagnostic specimen available for review

  • Needle aspirations or cytologies are not adequate
• No prior lymphoma, myelodysplastic syndromes, or leukemia (even if disease free ≥ 5 years)
• No CNS involvement

PATIENT CHARACTERISTICS:

Performance status

• Karnofsky 50-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal* (ULN) NOTE: *Unless due to Hodgkin's lymphoma

Renal

• Creatinine clearance ≥ 60 mL/min
• Creatinine ≤ 2.0 times ULN

Cardiovascular

• Ejection fraction ≥ 45% by 2-D echocardiogram
• No significant active cardiac disease

Pulmonary

• Adequate pulmonary function
• DLCO ≥ 45%

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• No known HIV or AIDS infection
• No active bacterial, fungal, or viral infection
• No medical condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Chemotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Poor Risk; Primary progressive, recurrent, or resistant relapse patients	Biological: filgrastim; 480 mcg beginning day +5; Drug: busulfan; 11.2 mg/kg; 0.8 mg/kg IV q6h X 14 doses; Drug: cyclophosphamide; 60 mg/kg IV over 2 hours x 2 days; Drug: etoposide; 60 mg/kg, IV; Drug: melphalan; 150mg/m2 in NS at a concentration of 0.4mg/cc infused over 60 minutes.; Procedure: autologous-autologous tandem hematopoietic stem cell transplantation; autologous-autologous tandem hematopoietic stem cell transplantation; Radiation: radiation therapy; radiation therapy
Experimental: Good Risk; First recurrence patients	Biological: filgrastim; 480 mcg beginning day +5; Drug: busulfan; 11.2 mg/kg; 0.8 mg/kg IV q6h X 14 doses; Drug: cyclophosphamide; 60 mg/kg IV over 2 hours x 2 days; Drug: etoposide; 60 mg/kg, IV; Drug: melphalan; 150mg/m2 in NS at a concentration of 0.4mg/cc infused over 60 minutes.; Procedure: autologous-autologous tandem hematopoietic stem cell transplantation; autologous-autologous tandem hematopoietic stem cell transplantation; Radiation: radiation therapy; radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Outcome is based on the number of patients who were alive without progression or relapse within 1 year. Progression is defined as a 50% increase in the sum of products of all measurable lesions.	one year after second transplant
Response Rate	Number of patients that receive a Complete Response (CR), Partial Response (PR)or Progression. CR defined as complete disappearance of all measurable and evaluable disease and no new lesions. PR is defined as >/= 50% decrease in the sum of products of all measurable lesions. Progression is defined as a 50% increase in the sum of products of all measurable lesions.	One year after second transplant
Number of Patients That Experience Pulmonary Toxicity	Pulmonary toxicity are due to side effects that medicinal drugs cause to the lungs.	One year after second transplant

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Brian J. Bolwell, MD, Cleveland Clinic Taussig Cancer Institute

Study record dates

Study Major Dates

• Study Start: February 1, 2002
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: December 14, 2005
• First Submitted That Met QC Criteria: December 14, 2005
• First Posted (Estimate): December 15, 2005

Study Record Updates

• Last Update Posted (Estimate): November 20, 2013
• Last Update Submitted That Met QC Criteria: October 28, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: recurrent adult Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclophosphamide; Etoposide; Melphalan; Busulfan
• Other Study ID Numbers: CCF5386; P30CA043703 (U.S. NIH Grant/Contract); CCF-5386 (Other Identifier: Cleveland Clinic IRB)