Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 18 to 65 FHCRC-336.3 NCI-V88-0470

Objectives

I.  Determine the feasibility of autologous bone marrow transplantation for 
patients with multiple myeloma that has progressed after conventional 
treatment.

II.  Determine the ability of peripheral blood stem cells or bone marrow from 
patients with multiple myeloma in partial remission to reconstitute 
hematopoiesis in vivo.

III.  Determine the effectiveness of busulfan/cyclophosphamide (BU/CTX) in 
producing remission.

IV.  Evaluate the toxicities of BU/CTX combined with antitumor necrosis factor 
alpha therapy in patients with multiple myeloma.

V.  Determine the duration of remission and survival of patients treated on 
this regimen.

Entry Criteria

Disease Characteristics:

Multiple myeloma as defined by the Salmon and Durie criteria

Any stage of disease allowed provided peripheral blood stem
cell (PBSC) and autologous bone marrow requirements are met

  Remission defined as complete disappearance of M-protein
  spike and/or urine globulin excretion irrespective of the
  level of plasma cells in the marrow

  Progressive disease on conventional treatment defined as
  rising M-protein spike or increasing urinary globulins, new
  or progressive bone lesions, rising serum calcium, or other
  objective data

Harvest of at least 1.5 x 10 to the eighth total nucleated bone
marrow cells/kg or equivalent PBSC required

  PBSC mobilization and harvest undertaken if criteria for
  bone marrow harvest cannot be met

  If in complete remission at marrow storage, transplantation
  is performed within 3 months after development of
  progressive disease provided a second response is unlikely

  Immediate transplantation allowed for patients with stable
  but persistent disease or progressive disease on treatment

At the time of marrow storage the following conditions apply:
  Peripheral blood count normal

  Less than 10% myeloma cells in the marrow

Syngeneic bone marrow transplantation allowed if suitable donor
is available

No suitable allogeneic donor available

Patient must be ineligible for or refuse treatment on
FHCRC-545.2

Prior/Concurrent Therapy:

See Disease Characteristics

Patient Characteristics:

Age:
  18 to 65

Performance status:
  Karnofsky 70-100%

Hematopoietic:
  (at the time of marrow storage)
  Peripheral granulocytes at least 2,000
  Platelets at least 100,000

Hepatic:
  Bilirubin less than 2.0 mg/dl
  GGT and GOT less than 2 x normal
  No significant hepatic disease that precludes administration
    of busulfan/cyclophosphamide

Renal:
  Creatinine clearance at least 50 ml/min
  Calcium no more than 15 mg/dl

Cardiovascular:
  LVEF at least 45% (required in patients with symptomatic
     cardiac disease)
  No significant cardiac disease that precludes administration
     of busulfan/cyclophosphamide

Pulmonary:
  No significant pulmonary disease that precludes
  administration of busulfan/cyclophosphamide

Expected Enrollment

At least 4 patients will be entered at each dose level studied.

Outline

Nonrandomized study.  Patients are treated on Regimen A, followed by 
maintenance therapy on Regimen B.

Regimen A:  Anti-Tumor Necrosis Factor Therapy followed by 2-Drug Combination 
Myeloablative Chemotherapy plus Hematopoietic Reconstitution.  Pentoxifylline, 
PTX; Ciprofloxacin, CPFX; followed by Busulfan, BU, NSC-750; Cyclophosphamide, 
CTX, NSC-26271; plus autologous or syngeneic bone marrow transplantation, BMT; 
or peripheral blood stem cell rescue, PBSC.

Regimen B:  Biological Response Modifier Therapy plus Single-Agent 
Chemotherapy.  Interferon alpha (supplier not specified), IFN-A; plus 
Dexamethasone, DM, NSC-34521.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

William Bensinger, MD, Protocol chair		Ph: 206-667-4933