Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment
|Multiple Myeloma||Drug: Dexamethasone Procedure: Tandem autologous stem cell transplant Drug: Cisplatin Drug: Doxorubicin Drug: Cyclophosphamide Drug: Etoposide Drug: Bortezomib Drug: Thalidomide Drug: Melphalan||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Tandem Autotransplantation for Multiple Myeloma in Participants With Less Than 12 Months of Preceding Therapy, Incorporating Velcade (Bortezomib) With the Transplant Chemotherapy and During Maintenance|
- Event-Free Survival (EFS) [ Time Frame: 8 years ]To determine whether, in comparison to Total Therapy II, the median Event-Free Survival (EFS) can be increased from 4.8 years to 7.2 years, which represents an increase in median EFS of approximately 50%, based on an intent-to-treat analysis.
- Identification of Drug Resistant Genes [ Time Frame: 5 years ]To determine whether repeated bone marrow samples analyzed for gene expression profiling (GEP) can identify genes related to drug resistance in myeloma. The drug resistant genes or the gene products might then be targeted specifically to eradicate myeloma cells surviving tandem transplantation.
- Number of Grade 3 Non-hematologic and Grade 4 Hematologic Serious Adverse Events Associated With the Addition of Bortezomib, Thalidomide, and Dexamethasone Into Autologous Transplant Regimens. [ Time Frame: 2 years ]To determine whether bortezomib, thalidomide and dexamethasone with transplant 1 and velcade/gemcitabine with transplant 2 can be safely incorporated into well-tested pre-transplant regimens of high-dose melphalan and carmustine/melphalan in doses equivalent to the BEAM(BCNU, etoposide, arabinoside, melphalan)regimen. Treatment-related toxicities will be compared to those reported in the literature using similar intensive approaches.
- Overall Survival [ Time Frame: 10 years ]To determine the median overall survival based on an intent-to-treat analysis, which should exceed 10 years, based on the projected 10-year survival of Total Therapy III, keeping in mind that participants are included in this protocol with up to 12 months of prior therapy.
|Actual Study Start Date:||May 2012|
|Study Completion Date:||August 2014|
|Primary Completion Date:||July 2013 (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.
Other Names:Procedure: Tandem autologous stem cell transplant Drug: Cisplatin
Other Names:Drug: Doxorubicin
Other Names:Drug: Cyclophosphamide
Given IV or PO
Other Names:Drug: Etoposide
Other Names:Drug: Bortezomib
Other Names:Drug: Thalidomide
Other Names:Drug: Melphalan
This study is targeted towards patients who have been diagnosed with Multiple Myeloma, POEMS(Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or myeloma plus amyloidosis and have had no more than 12 months of prior treatment. Furthermore, participants cannot have had a prior autologous or allogeneic transplant. 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 one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of participants with up to 12 months of prior treatment.
- Induction therapy has been reduced to a single cycle.
- Bortezomib and thalidomide have been added to the transplant regimen.
- Carmustine is added to the second transplant.
- Gemcitabine is added to the second transplant regimen.
- Consolidation treatment has been reduced to a single cycle.
- The first year of maintenance consists of 12 28-day cycles of bortezomib,dexamethasone, and either thalidomide, lenalidomide, or cyclophoshamide. The second year of maintenance therapy consists of lenalidomide and dexamethasone.
- The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation, consolidation, and maintenance.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01548573
|United States, Iowa|
|University of Iowa Holden Comprehensive Cancer Center|
|Iowa City, Iowa, United States, 52242|
|Principal Investigator:||Guido J Tricot, MD, PhD||University of Iowa|