Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Refractory Hodgkin's Disease or Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Hodgkin Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Combining more than one drug may kill more cancer cells. Bone
      marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of
      chemotherapy to kill more cancer cells.

      PURPOSE: This phase II trial is studying giving high-dose chemotherapy followed by bone
      marrow or peripheral stem cell transplantation to see how well it works in treating patients
      with refractory Hodgkin's disease or non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES: I. Determine the antitumor activity of intensive carmustine and etoposide with
      cisplatin or cyclophosphamide, followed by rescue with autologous bone marrow (ABM) treated
      in vitro with etoposide and/or peripheral blood stem cells mobilized with filgrastim (G-CSF)
      or sargramostim (GM-CSF) with or without radiotherapy in patients with refractory Hodgkin's
      disease or non-Hodgkin's lymphoma. II. Determine the time to recovery of peripheral blood
      counts in patients treated with this regimen. III. Correlate the rate of peripheral blood
      cell recovery in these patients with in vitro growth of ABM treated with etoposide.

      OUTLINE: This is a multicenter study. Autologous bone marrow (ABM) is harvested and
      two-thirds of the ABM is treated in vitro with etoposide (VP-16). ABM may have been stored
      earlier in the course of the disease for patients who are at high risk of relapse or who were
      previously treated with agents causing bone marrow or stem cell damage (e.g., nitrosoureas,
      pelvic irradiation). Patients with prior bone marrow involvement and subsequent bone marrow
      remission must have received 1 or 2 additional courses of the same chemotherapy before
      undergoing harvest of ABM. Patients for whom PBSC rescue alone is planned also undergo ABM
      harvest in case back-up ABM rescue is needed. Patients then receive sargramostim (GM-CSF) or
      filgrastim (G-CSF) subcutaneously beginning 5 days before harvest of peripheral blood stem
      cells (PBSC) and continuing until completion of harvest. Patients without extensive prior
      radiotherapy undergo radiotherapy to areas of measurable active disease plus a 2 cm margin on
      days -21 to -17 and -14 to -8. Patients without a contraindication to cisplatin (e.g.,
      hearing impairment, peripheral neuropathy) receive cisplatin IV over 3 hours on days -7 to -3
      and carmustine IV over 2 hours and VP-16 IV over 4 hours on days -6 to -4. Patients with a
      contraindication to cisplatin receive cyclophosphamide IV every 12 hours, VP-16 IV over 1
      hour every 12 hours, and carmustine IV over 1 hour on days -7 to -4. ABM and/or PBSC are
      reinfused on day 0. The first 6 ABM rescue patients receive untreated ABM and subsequent
      patients receive ABM treated in vitro with VP-16. Patients with bone marrow biopsy showing no
      evidence of regeneration (marrow cellularity less than 1%) at day 21 after PBSC rescue
      undergo back-up ABM rescue. Patients without engraftment (granulocyte count less than 500/mm3
      and untransfused platelets no greater than 20,000/mm3) by day 28 after rescue with ABM
      treated in vitro with VP-16 undergo rescue with untreated ABM.

      PROJECTED ACCRUAL: A total of 21-46 patients will be accrued for this study.
    

Intervention name(s): filgrastim; sargramostim; carmustine; cisplatin; cyclophosphamide; etoposide; autologous bone marrow transplantation; in vitro-treated bone marrow transplantation; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Procedure; Procedure; Procedure; Radiation
Intervention MeSH terms: Cyclophosphamide; Carmustine; Etoposide; Sargramostim
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Treatment
Keywords: recurrent adult Hodgkin lymphoma; adult lymphocyte predominant Hodgkin lymphoma; adult lymphocyte depletion Hodgkin lymphoma; adult nodular sclerosis Hodgkin lymphoma; adult mixed cellularity Hodgkin lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent adult Burkitt lymphoma; recurrent mantle cell lymphoma; recurrent small lymphocytic lymphoma