Tandem Transplantation in Multiple Myeloma (MM) Patients With <12 Months of Prior Treatment
The two objectives of this study are:
- To increase the 2-year event-free survival from 55%, established with Total Therapy II (UARK 98-026), to 75% in myeloma patients with cytogenetic abnormalities, and from 80%, established with the Total Therapy II regimen, to 95% in myeloma patients without cytogenetic abnormalities.
- To determine whether bortezomib, thalidomide, and dexamethasone can be safely incorporated with transplant 1 into the established pre-transplant regimen of high-dose melphalan (used in Total Therapy II) and whether Velcade and gemcitabine can be safely added to the transplant 2 high-dose chemotherapy regimen of combination melphalan and BCNU.
|Multiple Myeloma||Combination Product: tandem autologous transplantation||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Intervention Model Description:
Induction- Tandem Transplants with VTD-MEL and gemcitabine, BCNU, melphalan, velcade and dexamethasone- Maintenance therapyMasking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Tandem Autotransplantation for Multiple Myeloma Patients With Less Than 12 Months of Preceding Therapy, Incorporating Bortezomib With the Transplant Chemotherapy and During Maintenance|
- To Determine Whether, in Comparison to TT II, the Median EFS Can be Increased From 4.8 Years to 6.2 Years, Which Represents an Increase in Median EFS of Approximately 30% [ Time Frame: After enrollment of 204 subjects is completed ]
- In Assessing Patient Safety, we Will Examine Treatment Toxicity Related Mortality and SAEs. Historical Study Results Indicate That a Mortality Rate of Greater Than 10% is Not Acceptable in This Population, Nor is an SAE Rate of Greater Than 15%. [ Time Frame: Interim analyses for safety will be performed after 20, 100, 200, and 300 patients have been enrolled. ]
- Overall Survival Will be Compared to a Historical Control (UARK 98-026, TT2)as a Secondary Outcome. [ Time Frame: After 204 patients have been enrolled ]
|Study Start Date:||February 2008|
|Study Completion Date:||April 2014|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Experimental: Tandem autologous stem cell transplant
Induction: DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required.
After collection, participants will receive dexamethasone x 4 days every 14 days.
Transplant 1: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan.
Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days.
Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide) Transplant 2: 8 weeks to 6 months after the first transplant, participants will have the second transplant Maintenance: Year 1- VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles.
Combination Product: tandem autologous transplantation
DPACE: dexamethasone 20 mg days 1-4 and 8-11, cisplatin 10 mg/m2 days 1-4, Adriamycin 10 mg/m2 days 1-4, cyclophosphamide 400 mg/m2 days 1-4, etoposide 40 mg/m2 days 1-4.
Transplant 1: Dexamethasone 20 mg days -4 to -1 and +2 to +5. Velcade 1mg/m2 on days -4,-1, +2, and +5. Thalidomide 100mg on day -4 to day +5. Melphalan, 100 mg/m2 on days -4 and -1.
Transplant 2: Dexamethasone 20 mg on days -4 to -1 and +2 to +5. BCNU 300mg/m2 on day -4. Melphalan 140 mg/m2 on day -1. Velcade 1mg/m2 on days -4, -1, +2, +5. Gemcitabine 1000 mg/m2 on days -4 + -1.
Maintenance year 1: Bortezomib 1.0 mg/m2 on days 1, 4, 15,18 every cycle. Thalidomide, 100 mg . Dexamethasone,20 mg,on days 1-4 & 15-18 every cycle.
Maintenance year 2: Dexamethasone, 20 mg,days 1-4 every cycle.
This study is targeted towards patients who have been diagnosed with Multiple Myeloma and have had no prior autologous or allogeneic transplant. Furthermore, only up to 12 months of prior treatment are allowed in this patient population. The study schema consists of one round of induction chemotherapy, two transplants, one round of consolidation chemotherapy, and two years of maintenance treatment. This study design differs from its historical predecessors in the following manner:
- In contrast to Total Therapy II and III, which only allow enrollment of patients with at most one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of patients with up to 12 months of prior treatment. No statistically significant difference in outcome between patients with one or no cycle of preceding therapy and those with up to 12 months of prior therapy. This should allow enrollment of significantly more myeloma patients.
- Induction therapy has been reduced to a single cycle.
- Bortezomib and thalidomide have been added to the transplant regimen.
- BCNU is added to the second transplant to high dose melphalan.
- Gemcitabine is added to the second transplant regimen.
- Consolidation treatment has been reduced to a single cycle.
- The first year of maintenance is with bortezomib, thalidomide and dexamethasone, and the second year of maintenance therapy consists of dexamethasone only.
- The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation and maintenance.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00670631
|Principal Investigator:||Guido J Tricot, MD, PhD||University of Iowa|