Clinical trial NCT01548573
Conditions: Multiple Myeloma
Keywords: multiple myeloma POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) amyloidosis bone marrow transplant autologous
Sponsor: University of Iowa
Start date: 2012-05-01; Completion date: 2014-08-01
Enrollment: 19 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is designed to decrease toxicity associated with prior tandem transplant protocols by reducing the intensity of induction, consolidation and maintenance therapy, while increasing event-free survival by adding bortezomib (Velcade®), thalidomide, gemcitabine and carmustine to the transplant regimens to down-regulate the rescue of myeloma cells by the micro-environment and to prevent DNA repair post high-dose alkylating agent therapy. By reducing drug resistance, it is hoped that 3-year event-free survival will be increased significantly when compared to Total Therapy II. Additionally, participants will have the option of providing biospecimens for a sub-study evaluating gene expression profiling at specific timepoints to better understand drug-resistance in myeloma, and to determine whether there are genes or gene products in the resistant population that can be targeted by novel therapies.

Detailed description:
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.

Arms: arm 1: 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.
Interventions: intervention 1: Dexamethasone intervention 2: Tandem autologous stem cell transplant intervention 3: Cisplatin intervention 4: Doxorubicin intervention 5: Cyclophosphamide intervention 6: Etoposide intervention 7: Bortezomib intervention 8: Thalidomide intervention 9: Melphalan
Intervention descriptions: intervention 1: Given PO intervention 2: None intervention 3: Given IV intervention 4: Given IV intervention 5: Given IV or PO intervention 6: Given IV intervention 7: Given IV intervention 8: Given PO intervention 9: Given IV

Protocol documents: