Autologous or Syngeneic Stem Cell Transplant Followed by Donor Stem Cell Transplant and Bortezomib in Treating Patients With Newly Diagnosed High-Risk, Relapsed, or Refractory Multiple Myeloma
|ClinicalTrials.gov Identifier: NCT00793572|
Recruitment Status : Active, not recruiting
First Posted : November 19, 2008
Results First Posted : May 18, 2017
Last Update Posted : June 23, 2017
|Condition or disease||Intervention/treatment||Phase|
|Refractory Plasma Cell Myeloma||Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Bortezomib Drug: Cyclosporine Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Melphalan Drug: Mycophenolate Mofetil Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Procedure: Peripheral Blood Stem Cell Transplantation Procedure: Syngeneic Bone Marrow Transplantation Radiation: Total-Body Irradiation||Phase 2|
I. Progression-free survival (PFS) at 2 years after the autograft (=< 50% in historic controls).
I. Overall survival (OS) at 2 years after the autograft.
II. Non-relapse mortality (NRM) at 200 days and 1 year after allograft.
III. Incidence of grades II-IV acute graft-versus-host-disease (GVHD) and chronic extensive GVHD.
IV. Safety of bortezomib maintenance therapy after stem cell transplantation.
PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Patients undergo PBSC mobilization and collection using the preferred regimens at the participating institution.
CONDITIONING CHEMOTHERAPY AND AUTOLOGOUS OR SYNGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Patients receive high-dose melphalan intravenously (IV) on day -2 followed by an autologous or syngeneic HSCT on day 0.
NON-MYELOABLATIVE ALLOGENEIC HSCT: Beginning 40-180 days after autologous HSCT, patients receive 1 of the following regimens:
- HLA-IDENTICAL RELATED DONOR: Patients receive cyclosporine IV or orally (PO) twice daily (BID) starting on days -3 to 56, and taper until day 180. Patients then undergo total-body irradiation (TBI) and non-myeloablative allogeneic HSCT on day 0. Four to six hours after completion of allogeneic HSCT, patients receive mycophenolate mofetil (MMF) PO BID on days 0-27.
- HLA-UNRELATED DONOR: Patients receive fludarabine phosphate IV on days -4 to -2. Patients also receive cyclosporine IV or PO BID starting on days -3 to 100 and taper until day 180. Patients then undergo TBI and non-myeloablative allogeneic HSCT on day 0. Four to six hours after completion of allogeneic HSCT, patients receive MMF PO thrice daily (TID) on days 0-27 and then BID on days 27-40 with taper of MMF on days 40-96.
MAINTENANCE THERAPY: Beginning 60-120 days after allogeneic HSCT, patients receive bortezomib subcutaneously (SC) on days 1 and 4 of 14-day cycles for 9 months or for up to 18 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then annually for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Tandem Autologous HCT/Nonmyeloablative Allogeneic HCT From HLA-Matched Related and Unrelated Donors Followed by Bortezomib Maintenance Therapy for Patients With High-Risk Multiple Myeloma|
|Study Start Date :||October 2008|
|Primary Completion Date :||October 2016|
Experimental: Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
See Detailed Description
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Other Name: Autologous Stem Cell TransplantationDrug: Bortezomib
Other Names:Drug: Cyclosporine
Other Names:Drug: Cyclosporine
Other Names:Drug: Fludarabine Phosphate
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Melphalan
Other Names:Drug: Mycophenolate Mofetil
Other Names:Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Other Names:Procedure: Peripheral Blood Stem Cell Transplantation
Other Names:Procedure: Syngeneic Bone Marrow Transplantation
Undergo transplantationRadiation: Total-Body Irradiation
- Progression-free Survival [ Time Frame: At 2 years after the autograft ]
Confidence intervals will be estimated.
- Greater than 25% increase in serum (absolute increase must be ≥0.5 g/dL) or urine (absolute increase must be ≥200 mg/24h) M proteins compared to best response status after autologous transplant.
- Appearance of new lytic bone lesions or plasmacytomas.
- Incidence of Grades II-IV Acute GVHD [ Time Frame: 100 days post allo ]Confidence intervals will be estimated.
- Incidence of Chronic GVHD [ Time Frame: 1 year post allo ]Confidence intervals will be estimated.
- Incidence of Toxicities Related to Bortezomib Maintenance Therapy After the Stem Cell Transplantation [ Time Frame: Up to 100 days after the autograft or allograft ]Confidence intervals will be estimated.
- Non-relapse Mortality [ Time Frame: 200 and 365 days after allo ]Confidence intervals will be estimated. Assessed at 200 days and 1 year after allograft.
- OS [ Time Frame: At 2 years after the autograft ]Estimated by the method of Kaplan and Meier. Confidence intervals will be estimated.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00793572
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Marco Mielcarek||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|