A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.
I. To determine time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3
consecutive days), and platelet (> 20X 109^/L for 3 consecutive days).
2. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine
(fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune
suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin).
3. To determine the safety related to this combination in the first six months post
transplant, specifically, treatment related mortality and grade III and IV non hematologic
toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).
I. Incidence of myeloma progression in this high risk group of patients.
II. Incidence of transplant related mortality and morbidity.
III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive
IV. Incidence and severity of chronic GVHD.
V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex
virus (HSV), and Epstein-Barr virus (EBV) reactivation.
I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 & 2 years post
VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7
to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.
GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus
orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic
hematopoietic stem cell transplantation (HSCT) on day 0.
After completion of study treatment, patients are followed up for up to 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence and severity of acute GVHD using fludarabine phosphate / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and anti-thymocyte globulin
Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method.
First 6 months post-transplant
Barbara Ann Karmanos Cancer Institute
United States: Federal Government
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|