UARK 98-026 TT II: Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Thalidomide; Ara-C; BCNU; Cisplatin; Cytoxan; Dexamethasone; Doxorubicin; Etoposide; Filgrastim; Recombinant GM-CSF; Interferon-alpha-2b; Melphalan; Vincristine
Intervention description: All patients will be randomly assigned to receive thalidomide 400 mg as an oral, once daily dose throughout induction and 100mg between transplants after platelets are greater than 50,000μl and 200 mg post transplant consolidation, and a reduced dose of 100 mg on alternating days during the first year of maintenance and 50 mg qod thereafter versus no thalidomide. Thalidomide will be held during conditioning, transplant procedure, and recovery following transplant. It may be resumed once plateletrecovery is complete after each transplant; Cytarabine (Ara-C) 400 mg/m2 in 250 ml D5W over one hour daily for four days (on days -5, -4, -3, -2).
Start infusion 30 minutes after completion of BCNU on day -5.; Carmustine (BCNU) 300 mg/m2 in 1 liter of D5W in glass bottle (protect from light) to infuse over 2 hours on day -5. Check blood pressure every 15 minutes during infusion and 30 minutes after completion; Cisplatin* 15 mg/m2/day Continuous infusion 1-4 (DCEP CYCLE 2) Cisplatin* 7.5 mg/m2 Continuous infusion 1-4 (DPACE cycle)
*Cisplatin doses will be modified for renal insufficiency as follows: Cisplatin dose Creatinine 15 mg/m2 (full dose) < 1.5 mg/dl 10 mg/m2 1.6 - 2.0 mg/dl 7.5 mg/m2 2.1 - 3.0 mg/dl 0 mg (hold Cisplatin) > 3.0 mg/dl; Cycle 2 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cycle 3 - CAD and PBSC Collection #1 Cyclophosphamide 750 mg/m2/day Continuous infusion 1-4 Cycle 4 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cytoxan/VP-16 and PBSC Collection-Cyclophosphamide 2 grams/m2 (Total dose 4 gm/m2) IV by CI 1 and 2 Post-Transplant Consolidation-Cyclophosphamide 300 mg/m2 Continuous infusion 1-4; Induction cycle 1 VAD Dexamethasone 40 mg/day PO 1-4, 9-12, 17-20 Cycle 2 - DCEP Dexamethasone 40 mg/day PO 1-4 Cycle 3 - CAD and PBSC Collection #1 Dexamethasone 40 mg/day PO 1-4 Cycle 4 - DCEP and PBSC Collection #2 Dexamethasone 40 mg/day PO 1-4 Post-Transplant Consolidation Dexamethasone 40 mg PO 1-4 Dexamethasone Consolidation Patients that do not achieve adequate platelet recovery (defined as < 80,000/μl) will receive consolidation with Dexamethasone 40 mg x 4 days every 28 days for 1 year Maintenance year one Dexamethasone 40 mg PO q 3 months, day 1-4, 9-12, 17-20; Doxorubicin may be further diluted in 5% dextrose or sodium chloride injection and should be administered slowly into tubing of a freely flowing intravenous infusion with great care taken to avoid extravasation.; Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days; G-CSF will be administered at a dose of 10mcg/kg or GM-CSF at a dose of 10 mcg/kg. G-CSF or GM-CSF will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.; GM-CSF at a dose of 10 μg/kg SC, divided in 2 doses each day, will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.; AGENT DOSE ROUTE DAYS Intron-A 3 million units/m2 SQ TIW Thalidomide (for those randomized at initial registration) 50 mg QOD PO Every other day (qod; Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days; Formulation: 1 mg/1 ml, 2 mg/2 ml, and 5 mg/ 5 ml vials. Vincristine should be administered intravenously through a freely-running IV. If it extravasates, it produces a severe local reaction with skin slough. FATAL IF GIVEN INTRATHECALLY, FOR INTRAVENOUS USE ONLY.
Intervention MeSH terms: Interferons; Cytarabine; Interferon-alpha; Interferon alpha-2; Thalidomide; Dexamethasone; Cyclophosphamide; Melphalan; Carmustine; Cisplatin; Doxorubicin; Etoposide; Vincristine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 668.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Cancer; Therapy; Thalidomide; DTPACE; Transplant; VAD; DCEP; CAD; Consolidation; Melphalan

Summary:

      This study has been designed to evaluate whether "anti-angiogenesis" therapy with thalidomide
      and whether additional chemotherapy after transplant will be beneficial. Another objective is
      to find out what kinds of side effects occur with this combination of treatment and how often
      they occur.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have newly diagnosed active multiple myeloma requiring treatment.
             Patients with a previous history of smoldering myeloma will be eligible if there is
             evidence of progressive disease requiring chemotherapy.

          -  Protein criteria must be present in order to evaluate response.Non-secretory patients
             are eligible provided the patient has > or = 20% plasmacytosis or multiple (>3) focal
             plasmacytomas on MRI or diffuse hyperintense signal on STIR images in the absence of
             hematopoietic growth factors is seen.

          -  All necessary baseline studies for determining stage, bloodwork, and bone marrow must
             be obtained within 35 days prior to registration.

          -  Patients must have received no more than one cycle of prior chemotherapy including one
             month of Dexamethasone and Thalidomide for this disease. Patients may have received
             prior radiotherapy provided approval has been obtained by one of the study
             coordinators.

          -  Patients must have a performance status of 0-2 based on SWOG criteria. Patients with a
             poor performance status (3-4), based solely on bone pain, will be eligible.

          -  Patients with renal failure, even if on dialysis, are eligible if it is felt to be due
             to myeloma and if the duration of renal failure does not exceed two months

          -  Patients must be 75 years of age or less at the time of registration

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines.

          -  If medically appropriate, patients with pathologic fractures, pneumonia at diagnosis
             or hyperviscosity with shortness of breath should have these conditions attended to
             prior to registration.

        Exclusion Criteria:

          -  Patients must not have significant co-morbid medical conditions or uncontrolled life
             threatening infection

          -  Patients must not have uncontrolled diabetes

          -  Patients with recent (< or =6 months) myocardial infarction, unstable angina,
             difficult to control congestive heart failure, uncontrolled hypertension, or difficult
             to control cardiac arrythmias are ineligible. Ejection fraction by ECHO or MUGA should
             be within the institutional normal range and must be performed within 42 days prior to
             registration.

          -  Patients must not have a history of chronic obstructive or chronic restrictive
             pulmonary disease.

          -  No prior malignancy is allowed except for adequately treated basal cell or squamous
             cell skin cancer, in situ cervical cancer, or other cancer for which the patient has
             been disease free for at least three years.Prior malignancy is acceptable provided
             there has been no evidence of disease within the three-year interval and there must be
             no prior treatment with cytotoxic drugs that could potentially be assigned on this
             treatment protocol.

          -  Pregnant or nursing women may not participate. Women of child-bearing potential must
             have a negative pregnancy documented within one week of registration. Women/men of
             reproductive potential may not participate unless they have agreed to use two forms of
             effective contraceptive method.