UARK 89-001 Phase II Study of Intensive "TOTAL THERAPY" For Untreated or Minimally Treated Patients With Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: VAD; High-Dose cyclophosphamide; Hemopoietic stem cell procurement; EDAP; Autologous Hemopoietic Stem Cell Transplant 1; Autologous Hemopoietic Stem Cell Transplant 2; Maintenance
Intervention description: 3 Cycles (3rd cycle optional): Vincristine 0.5 mg/d d 1 - 4 CI Adriamycin 10 mg/m2/d d 1 - 4 CI Dexamethasone 40 mg/d d 1-4, 9-12, 17-20; Approximately 5-6 weeks after VAD 2 or 3:
Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1; Collection target = 10 x 10^6 cells/kg; Approximately 5-6 weeks after high-dose cyclophosphamide Etoposide 100 mg/m2/d d 1 - 4 CI Cisplatin 25 mg/m2/d d 1 - 4 CI Ara C l g/m2 d 5 Dexamethasone 40 mg d 1-5; 4-6 weeks after EDAP: Melphalan 100 mg/m2 days -1 and -2; 4-6 months after Transplant 1: Melphalan 100 mg/m2 days -1 and -2; 3 months after Transplant 2: Intron A 3 X 10^6 units /m2 M-W-F subcutaneously until relapse
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 231.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This experimental study evaluates the effects of a series of intensive drug regimens as
      initial treatment for Multiple Myeloma followed by 2 bone marrow transplantations 4-6 months
      apart in support of high-dose Melphalan, followed by Interferon treatment indefinitely.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously untreated patients with the diagnosis of multiple myeloma are eligible.
             Similarly, patients who have not had more than one cycle of standard chemotherapy or
             up to one month of interferon and/or glucocorticoids are eligible.

          -  Patients must have objective evidence of, or be symptomatic from, complications due to
             myeloma (e.g., bone pain from fractures, weakness from anemia). Asymptomatic patients
             may be treated only if the diagnosis is confirmed and if there is evidence of
             increasing tumor mass (e.g., rising myeloma protein and/or increasing lytic lesions).

          -  Asymptomatic patients with idiopathic monoclonal peaks, localized plasmacytomas, or
             indolent, asymptomatic myeloma are not eligible for this study. Any patient without
             documented increasing disease and/or clearly symptomatic disease is not eligible.

          -  Measurable, direct manifestations of myeloma must be present, such as monoclonal serum
             or urine globulins. Plasma cell tumors must also be documented. Patients without
             protein criteria are eligible if bone marrow has > 30% plasmacytosis documented by
             bilateral bone marrow aspirations and biopsies.

          -  Patients with all stages of multiple myeloma (I, II, III) are eligible. Necessary
             baseline studies must be obtained to determine the stage prior to registration.

          -  Patients may have received local radiation to painful compression fractures or lytic
             bone lesions, provided that adequate autologous bone marrow can still be harvested.
             Patients presenting with clinical conditions requiring radiotherapy (e.g. spinal cord
             compression) may proceed with concurrent local radiation and VAD. Should compression
             fractures of known prestudy lytic lesions occur during later, more myelosuppressive
             phases of induction therapy, radiotherapy should be completed first prior to
             proceeding with high-dose cyclophosphamide, EDAP or melphalan.

          -  Patients should be older than 15 years of age and may be up to 65 years old.

          -  Pregnant females are excluded from study.

          -  Eligibility criteria change with the progress through the different phases of the
             induction program towards the two cycles of marrow-ablative therapy. These are
             summarized in the eligibility checklist.

          -  Briefly, prior to VAD, patients must have a normal cardiac ejection fraction of > 50%
             (on ECHO cardiography or MUGGA scan), and fairly normal liver function tests
             (bilirubin < 2 mg% and serum transaminase levels less than 2 x normal). Screening for
             viral hepatitis should be negative for acute or chronic active hepatitis. Positive
             antibody (anti-HAV, HBSAb) suggestive of remote exposure is acceptable. However,
             patients who test positive for Hepatitis C antibody (anti-HCV) or HIV are ineligible.
             Those with renal failure are eligible and should start VAD promptly and receive
             additional medical measures as needed. Patients presenting with infections upon
             presentation shall receive proper medical management prior to starting therapy.
             Patient's performance status is not a criterion for entry on the VAD portion of this
             program.

          -  After 2 or 3 cycles of VAD, serum creatinine levels must be 2 mg% and carbon monoxide
             diffusion capacity 50%. Cardiac and liver function requirements as with VAD.

          -  Not until reaching the high-dose melphalan stage of 70 mg/M2 will there be a
             requirement for Zubrod performance of 0 and 1 which must also be fulfilled with each
             of the 2 marrow-ablative doses of melphalan (200 mg/M2).

        Exclusion Criteria:

          -  Less than 10 x 108 cells/kg stored.

          -  a granulocyte count of less than 1500/µl and a platelet count less than 150,000/µl.