UARK 2006-15: A Study of Tandem Transplants With or Without Bortezomib and Thalidomide
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Interim/Maintenance Dexamethasone; Induction/Consolidation Dexamethasone; Induction/Consolidation Cisplatin; Induction/Consolidation Adriamycin; InductionConsolidation Cyclophosphamide; Induction/Consolidation Etoposide; Induction Pegfilgrastim; Transplant 1 Dexamethasone; Transplant 1 Cisplatin; Transplant 1 Adriamycin; Transplant 1 Cyclophosphamide; Transplant 1 Etoposide; Transplant 1 Melphalan; Transplant 1 and 2 Pegfilgrastim; Autologous Peripheral Blood Stem Cell Transplant (ASCT); Transplant 2 Carmustine; Transplant 2 Etoposide; Transplant 2 Cytarabine; Transplant 2 Melphalan; Transplant 2 Dexamethasone; Transplant 1 and 2 Bortezomib; Transplant 1 and 2 Thalidomide
Intervention description: 20 mg Days 1-4 every 3 weeks in the interim between treatment phases and during maintenance; 40 mg Days 1-4; 10 mg/m2 by continuous infusion Days 1-4; 10 mg/m2 by continuous infusion Days 1-4; 400 mg/m2 by continuous infusion Days 1-4; 40 mg/m2 by continuous infusion Days 1-4; 6 mg Days 6 and 13; 20 mg Days -4, -3, -2, -1 and +4, +5, +6, and +7; 20 mg/m2 by continuous infusion Days -3 and -2; 20 mg/m2 by continuous infusion Days -3 and -2; 800 mg/m2 by continuous infusion Days -3 and -2; 80 mg/m2 by continuous infusion Days -3 and -2; 50 mg/m2 Days -2 and -1; 6 mg Day +6; Day 0; 300 mg/m2 Day -5; 200 mg/m2 Days -5, -4, -3, -2; 400 mg/m2 Days -5, -4, -3, -2; 140 mg/m2 Day -1; 20 mg Days -5, -4, -3, -2, +4, +5, +6, +7; 1 mg/m2 Days -4, -1, +3, +7; 200 mg Days -4 to +5
Intervention MeSH terms: Cytarabine; Thalidomide; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Melphalan; Carmustine; Cisplatin; Etoposide; Etoposide phosphate; Doxorubicin; Liposomal doxorubicin; Bortezomib; BB 1101
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Add three drugs, bortezomib, thalidomide, and dexamethasone (VTD) to the high dose
      chemotherapy regimen immediately before transplant (DPACE/Melphalan) to try to improve
      myeloma response and acquire longer survival for participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with symptomatic multiple myeloma, sensitive or refractory to at least one
             prior line of chemotherapy.

          -  Karnofsky performance score > 60%, unless due to MM.

          -  Patients must be <75 years of age at the time of registration.

          -  Patient must not have had a prior auto- or allotransplant.

          -  Patient must have signed an IRB-approved informed consent and understand the
             investigational nature of the study.

          -  Negative serology for HIV.

          -  Baseline biopsies and laboratory studies are to be completed within 35 days of
             registration, within 60 days for scans and radiological studies; patients must not
             have a history of severe chronic obstructive or chronic restrictive pulmonary disease.
             Patients must have adequate pulmonary function studies > 50% of predicted on
             mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of predicted.
             Patients unable to complete pulmonary function tests because of myeloma-related chest
             pain, must have a high resolution CT scan of the chest and must also have acceptable
             arterial blood gases defined as P02 greater than 70.

          -  Patients with recent (< 6 months) myocardial infarction, unstable angina, difficult to
             control congestive heart failure, uncontrolled hypertension, or difficult to control
             cardiac arrhythmias are ineligible. Ejection fraction by ECHO or MUGA must be > 40%
             and must be performed within 60 days prior to registration, unless the patient has
             received chemotherapy within that period of time (dexamethasone and thalidomide
             excluded), in which case the LVEF must be repeated.

          -  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 or if the
             malignancy is considered much less life threatening than the myeloma.

          -  Pregnant or nursing women may not participate. Women of childbearing 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 an effective
             contraceptive method.

          -  Patients must be able to receive full doses of D PACE, in the opinion of the treating
             investigator, with the exception that patients with creatinine clearance 30-50 ml/min
             will receive only 50% of the cisplatin dose.

        Exclusion Criteria:

          -  Fever or active infection requiring intravenous antibiotic, defined as fever or
             antibiotics within 72 hours from baseline.

          -  Severe renal dysfunction, defined as a creatinine > 3mg/dl or a creatinine clearance
             of < 30ml/min.

          -  Significant neurotoxicity, defined as grade > 3 neurotoxicity per NCI Common Toxicity
             Criteria (See Appendix).

          -  Platelet count < 100,000/mm^3, or ANC < 1,000/μl

          -  POEMS Syndrome.

          -  Clinically significant hepatic dysfunction as noted by direct bilirubin or AST >3
             times the upper normal limit or clinically significant concurrent hepatitis.

          -  New York Hospital Association (NYHA) Class III or Class IV heart failure.

          -  Myocardial infarction within the last 6 months.

          -  Patients with a history of treatment for clinically significant ventricular cardiac
             arrhythmias.

          -  Poorly-controlled hypertension, diabetes mellitus, or other serious medical illness or
             psychiatric illness that could potentially interfere with the completion of treatment
             according to this protocol.

          -  Prior adriamycin exposure >450 mg/m^2

          -  Prior exposure to thalidomide which resulted in severe toxicity requiring drug
             discontinuation.