Neoplasms

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Multiple Myeloma

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Monoclonal Gammopathy of Undetermined Significance

Endocrine System Diseases

Neoplasms by Histologic Type

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Antineoplastic Agents

All Drugs and Chemicals

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Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Amino Acids

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Dexamethasone

Melphalan

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Bortezomib

Dexamethasone acetate

BB 1101

Etoposide phosphate

Thalidomide

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Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

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Antineoplastic Agents, Hormonal

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Enzyme Inhibitors

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Growth Inhibitors

Phenylalanine

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.

Tandem autologous stem cell transplant

Guido J Tricot, MD, PhD

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.

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.

Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment

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

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.

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.

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.

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.

National Cancer Institute (NCI)

University of Iowa

Director, Holden Cancer Center Bone Marrow Transplant and Myeloma Program

This was a single arm study for myeloma patients with \<12 months of prior treatment to determine whether the incorporation of bortezomib into a tandem transplant regimen followed by 2 years of maintenance therapy would increase event-free survival.

Tandem Transplant in MM <12 Mos of Prior Treatment

Enrollment halted prematurely. Study met stopping rules. Outcomes will not be tracked and published

Age, Categorical

Age, Continuous

Enrollment halted prematurely. Study met stopping rules. Outcomes will not be tracked and published.

Sex: Female, Male

United States

Region of Enrollment

Guido Tricot, MD, PhD

Induction and PBSC Collection:1 cycle of combination D-PACE (and peripheral blood stem cell collection. After collection, participants may receive interim dexamethasone at 20mg days 1-4 every 14 days.

Transplant 1: 6 weeks after first day of D-PACE , but can occur as early as 4 weeks and as late as 6 months. Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days.

Transplant 2: 8 weeks-6 months after the first transplant, participants will have second transplant. Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days.

Consolidation Phase (if administered): 4 weeks-4 months after second transplant, participants may receive consolidation chemotherapy.

Maintenance Phase year 1 and 2:The first year of maintenance will commence between 6 weeks-6 months after consolidation or 4 weeks-6 months after transplant if consolidation is skipped.

DP

Tandem Autologous Stem Cell Transplant

Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity).

Data for outcome measure 1 were not collected.

Event-Free Survival (EFS)

Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity).

Data for outcome measure 2 were not collected.

Identification of Drug Resistant Genes

Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity).

Data for outcome measure 3 were not collected.

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.

Enrollment halted prematurely. Study met stopping rules (3 or more of the first 20 participants died due to treatment-related toxicity).

Data for outcome measure 4 were not collected.

Overall Survival

Overall Study

Spots Global Cancer Trial Database for tandem autologous stem cell transplant