UARK 2012-02 Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: myPRS; Induction 1 - MEL-10+CFZ-TD-PACE; First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic); Inter-Therapy - MEL-20+CFZ-TD-PACE (75%); Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic); Consolidation - CFZ-TD-PACE; Maintenance - CFZ-R(T)-D
Intervention description: Genome expression profiling used to identify high-risk and low-risk multiple myeloma; Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given.
Regimen: CFZ 20 mg/m2 on days 1, 5, & 6; MEL 10mg/m2 on day 3; T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 400 mg/m2/d, and E 40 mg/m2/d on days 5-8; G-CSF 10 mcg/kg/day from day 11 through end of Peripheral Blood Stem Cell (PBSC) collection.
Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until 1st transplant.; Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given.
Regimen: CFZ 20 mg/m2 on days -5 & -4; MEL 20 mg/m2/d, T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 100 mg/m2/d, and E 80 mg/m2/d on days -5 & -2; PBSC transplant on day 0.
Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until inter-therapy.; Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given.
Regimen: CFZ 27 mg/m2 on days 1-2; MEL 5 mg/m2/d, T 200 mg/d, D 20 mg/d, P 7.5 mg/m2/d, A 7.5 mg/m2/d, C 75 mg/m2/d, and E 60 mg/m2/d on days 1-4.
Optional Bridging with T 50 mg/d and D 20 mg on day 1-4 every 21 days until 2nd transplant.; Melphalan (MEL) and Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and Dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), Adriamycin (A), Cyclophosphamide (C) and Etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter. After completion of the continuous chemotherapy, Granulocyte colony-stimulating factor (G-CSF), a shot just under the skin to help the bone marrow and blood counts recover more quickly after chemotherapy, will be given.
Regimen: CFZ 20 mg/m2 on days -5 & -4; MEL 20 mg/m2/d, T 200 mg/d, D 40 mg/d, P 10 mg/m2/d, A 10 mg/m2/d, C 100 mg/m2/d, and E 80 mg/m2/d on days -5 & -2; PBSC transplant on day 0.
Optional Bridging with T 50mg/d and D 20 mg on day 1-4 every 21 days until consolidation.; Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) is a capsule and dexamethasone (D) is a pill; both will be taken by mouth. Cisplatin (P), adriamycin (A), cyclophosphamide (C) and etoposide (E) are all given into the vein (IV) by a continuous infusion through a central catheter.
Regimen: CFZ 27 mg/m2 on days 1-2; T 200 mg/d, D 40 mg/d, P 7.5 mg/m2/d, A 7.5 mg/m2/d, C 300 mg/m2/d, and E 30 mg/m2/d on days 1-4.; Carfilzomib (CFZ) will be given into a central venous catheter. Thalidomide (T) and lenalidomide (R) are capsules and dexamethasone (D) is a pill; all will be taken by mouth.
Regimen: For Cycles 1-12 CFZ 27 mg/m2/wk and D 12 mg/wk on days 1, 8, 15, & 22; lenalidomide (R) 15 mg/d on days 1-21. For Cycles 13-24 CFZ 27 mg/m2/wk and D 12 mg/wk on days 1, 8, 15, & 22. T may be substituted for R at 100 mg/day at the treating physician's discretion.
Intervention MeSH terms: Thalidomide; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Melphalan; Cisplatin; Doxorubicin; Liposomal doxorubicin; Etoposide; Etoposide phosphate; Lenalidomide; Lenograstim; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: High-Risk; Carfilzomib

Summary:

      The purpose of this study is to improve the clinical outcomes of research subjects with
      high-risk multiple myeloma in the context of the immediately preceding Total therapy 5 trial
      2008-02 and Total therapy 3 trials 2003-33 and 2006-66.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have newly diagnosed active MM requiring treatment. Patients with a
             previous history of smoldering myeloma will be eligible if there is evidence of
             progressive disease requiring chemotherapy.

          -  Patients must be either untreated or have not had more than one cycle of systemic MM
             therapy, excluding bisphosphonates and localized radiation.

          -  Participants must have high-risk disease, as defined by GEP70 risk score of ≥ 0.66

          -  Zubrod ≤ 2, unless solely due to symptoms of MM-related bone disease.

          -  Patients must have a platelet count of ≥ 50,000/μL, unless lower levels are explained
             by extensive bone marrow plasmacytosis.

          -  Patients must be at least 18 years of age and not older than 75 years of age at the
             time of registration.

          -  Participants must have preserved renal function as defined by a serum creatinine level
             of < 3 mg/dL.

          -  Participants must have an ejection fraction by ECHO or MUGA scan ≥ 45%

          -  Patients must have adequate pulmonary function studies > 50% of predicted on
             mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of predicted.
             If the patient is unable to complete pulmonary function tests due to MM related pain
             or condition, exception may be granted if the principal investigator documents that
             the patient is a candidate for high dose therapy.

          -  Patients must have signed an IRB-approved informed consent indicating their
             understanding of the proposed treatment and understanding that the protocol has been
             approved by the IRB.

        Exclusion Criteria:

          -  Does not have high-risk disease

          -  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.

          -  Patients must not have prior malignancy, except for adequately treated basal cell or
             squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
             patient has not received treatment for one year prior to enrollment. Other cancers
             will only be acceptable if the patient's life expectancy exceeds five years.

          -  Pregnant or nursing women may not participate. Women of childbearing potential must
             have a negative pregnancy documented within one week of registration. Subjects of
             reproductive potential may not participate unless they have agreed to use an effective
             contraceptive method.