NCT02128230

UARK 2012-02 Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission

A Phase II Trial For High-Risk Myeloma Evaluating Accelerating and Sustaining Complete Remission (AS-CR) by Applying Non-Host-Exhausting and Timely Dose-Reduced Mel-80-CFZ-TD-Pace Transplant(s) With Interspersed Mel-20-CFZ-TD-Pace With CFZ-RD and CFZ-D Maintenance

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University of Arkansas · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Total therapy 5B will attempt to accelerate and sustain, at 2 years from starting therapy, the proportion of subjects in complete remission by reducing host-imposed toxicity and facilitating timely completion of highly synergistic 8-drug combination therapy, including the next generation proteasome inhibitor, Carfilzomib. This will result in avoiding multiple myeloma re-growth that, we postulate, ensued in Total therapy 3 during recovery phases from severe de-conditioning. It is speculated that the incidence of positive minimal residual disease will be reduced with the addition of one cycle of consolidation therapy. The following approach will be implemented: * apply a 4-day fractionated lower dose melphalan (80 mg/m2) together with CFZ-TD-PACE regimen in MEL80-CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE as a hopefully less toxic and more effective transplant regimen * interspersed with 1 cycle of non-transplant supported MEL-20-CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE (in lower doses than with transplant) inter-therapy (reduced from two cycles due to prolonged thrombocytopenia) * followed by CFZ-TD (carfilzomib, thalidomide, dexamethasone) PACE consolidation therapy post transplant #2 * CFZ-RD (carfilzomib, lenalidomide and dexamethasone) maintenance for 1 year followed by CFZ-D for an additional year

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DEVICE	myPRS	Genome expression profiling used to identify high-risk and low-risk multiple myeloma
DRUG	Induction 1 - MEL-10+CFZ-TD-PACE	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.
DRUG	First Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)	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.
DRUG	Inter-Therapy - MEL-20+CFZ-TD-PACE (75%)	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.
DRUG	Second Transplant - MEL-80+CFZ-TD-PACE + PBSC (biologic)	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.
DRUG	Consolidation - CFZ-TD-PACE	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.
DRUG	Maintenance - CFZ-R(T)-D	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.

Timeline

• Start date: 2014-06-10
• Primary completion: 2019-02-19
• Completion: 2019-02-19
• First posted: 2014-05-01
• Last updated: 2021-06-22
• Results posted: 2021-06-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study