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

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: melphalan; Drug: cyclophosphamide; Biological: filgrastim; Drug: busulfan; Drug: etoposide; Procedure: autologous-autologous tandem hematopoietic stem cell transplantation; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00265889

CCF5386

P30CA043703 (U.S. NIH Grant/Contract)

CCF-5386 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

Poor Risk

Experimental group

Description:

Primary progressive, recurrent, or resistant relapse patients

Treatment:

Drug: etoposide

Drug: busulfan

Radiation: radiation therapy

Drug: cyclophosphamide

Biological: filgrastim

Procedure: autologous-autologous tandem hematopoietic stem cell transplantation

Drug: melphalan

Good Risk

Experimental group

Description:

First recurrence patients

Treatment:

Drug: etoposide

Drug: busulfan

Radiation: radiation therapy

Drug: cyclophosphamide

Biological: filgrastim

Procedure: autologous-autologous tandem hematopoietic stem cell transplantation

Drug: melphalan