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
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|ClinicalTrials.gov Identifier: NCT00793572|
Recruitment Status : Completed
First Posted : November 19, 2008
Results First Posted : May 18, 2017
Last Update Posted : January 22, 2020
|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|
|Actual Study Start Date :||October 2008|
|Actual Primary Completion Date :||October 2016|
|Actual Study 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 Transplantation
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
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
- Number of Patients Surviving Progression-free [ Time Frame: At 2 years after the autograft ]
Number of subjects surviving without progressive disease post-transplant.
Progressive disease criteria:
- 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.
- Number of Patients With Grade II-IV Acute GVHD [ Time Frame: 100 days post allo transplant ]
Number of patients who developed acute GVHD post allogeneic transplant.
- - a maculopapular eruption involving < 25% BSA
- - a maculopapular eruption involving 25 - 50% BSA
- - generalized erythroderma
- - generalized erythroderma w/ bullous formation and often w/ desquamation
- - bilirubin 2.0 - 3.0 mg/100 mL
- - bilirubin 3 - 5.9 mg/100 mL
- - bilirubin 6 - 14.9 mg/100 mL
- - bilirubin > 15 mg/100 mL
Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall.
aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
- Number of Patients With Chronic GVHD [ Time Frame: 1 year post allo ]Number of subjects with classic chronic or chronic extensive GVHD post allogeneic transplant.
- Number of Patients With Toxicities Related to Bortezomib Maintenance Therapy [ Time Frame: Up to 100 days after the autograft or allograft ]Number of subjects with toxicities related to bortezomib maintenance therapy post-transplant.
- Number of Patients With Non-relapse Mortality [ Time Frame: 200 and 365 days after allo ]Number of subjects with non-relapse mortalities post allogeneic transplant.
- Number of Patients Surviving Overall [ Time Frame: At 2 years after the autograft ]Number of subjects surviving two years post autologous transplant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|