High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant
|Refractory Multiple Myeloma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma||Other: pharmacological study Drug: tacrolimus Drug: sirolimus Biological: anti-thymocyte globulin Drug: fludarabine phosphate Drug: busulfan Drug: bortezomib Procedure: allogeneic hematopoietic stem cell transplantation Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.|
- Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin [ Time Frame: First 6 months post-transplant ]Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method.
- Time to Platelet Absolute Neutrophil Recovery (Engraftment) [ Time Frame: First 6 months post-transplant ]Estimated using Kaplan-Meier method.
- Treatment Related Mortality Defined as Death in Continuous or Complete Remission [ Time Frame: From the date of transplant to the date of death, assessed up to 6 months post transplant ]Based on National Cancer Institute (NCI) CTCAE version 4.
- Grade III and IV Non Hematologic Toxicities [ Time Frame: First 6 months post transplant ]Based on NCI CTCAE version 4.
- Incidence of Myeloma Progression [ Time Frame: Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant ]
- Incidence of Transplant Related Mortality and Morbidity [ Time Frame: Up to 2 years post transplant ]
- Incidence of TTP [ Time Frame: Up to 2 years post transplant ]
- Incidence of SOS [ Time Frame: Up to 2 years post transplant ]
- Incidence and Severity of Chronic GVHD [ Time Frame: Up to 2 years post transplant ]
- Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation [ Time Frame: Weekly to day 100 ]
- Overall Survival [ Time Frame: Up to 2 years post transplant ]
- Progression Free Survival [ Time Frame: From the day of transplant to progression, death, or last contact, assessed up to 2 years ]
- Recovery of T-cell, B Cell and NK Cell Phenotypes [ Time Frame: Days 30, 60, 90, and at 6 months after transplant ]
|Study Start Date:||February 2012|
|Study Completion Date:||May 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy, enzyme inhibitor)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.
GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0.
Other: pharmacological study
Other Name: pharmacological studiesDrug: tacrolimus
Other Names:Drug: sirolimus
Other Names:Biological: anti-thymocyte globulin
Other Names:Drug: fludarabine phosphate
Other Names:Drug: busulfan
Other Names:Drug: bortezomib
Other Names:Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic HSCTOther: laboratory biomarker analysis
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 syndrome (SOS).
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 transplant.
VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01534143
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|Principal Investigator:||Zaid Al-Kadhimi||Barbara Ann Karmanos Cancer Institute|