Clinical trial NCT01860170
Conditions: Hematological Malignancy
Keywords: Blood and Marrow Transplant (BMT) MRD MUD GVHD
Sponsor: Spectrum Health Hospitals
Start date: 2012-04-01; Completion date: 2018-03-01
Enrollment: 28 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine if Bortezomib, known commercially as Velcade is safe and tolerated at different dose levels (amounts) with high dose Cyclophosphamide to be used as graft versus host disease prevention after reduced-intensity allogeneic hematopoietic stem cell transplantation.

Detailed description:
It is hypothesized that the administration of an early and short course cyclophosphamide and bortezomib after allogeneic hematopoietic stem cell transplantationin in the setting of matched related or unrelated donor transplantation using a standard reduced-intensity conditioning regimen is feasible.

The study is a phase I study. The primary objective of the study is to determine the feasibility and safety of increasing doses of bortezomib administered post-transplant in conjunction with fixed high dose cyclophosphamide, also administered post-transplant in the setting of reduced-intensity allogeneic hematopoietic stem cell transplant, as GVHD prophylaxis strategy. Eligible patients will receive a conditioning regimen based on a combination of fludarabine and busulfan with or without rATG.

Arms: arm 1: Bortezomib (Velcade®) 0.7 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3. arm 2: Bortezomib (Velcade®) 1 mg/ m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3. arm 3: Bortezomib (Velcade®) 1.3 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.
Interventions: intervention 1: Cohort 1-Bortezomib (Velcade ®) intervention 2: Cohort 2-Bortezomib (Velcade ®) intervention 3: Cohort 3-Bortezomib (Velcade ®)
Intervention descriptions: intervention 1: Conditioning Regimen: Fludarabine 30 mg/m2 on days -7, -6, -5, -4, -3 and -2; Busulfan 0.8 mg/kg, every 6 hours on days -3 and -2; Patients with matched unrelated donor also receive rATG (Thymoglobulin ®) 2 mg/kg on days -4, -3, -2 and -1.

Cyclophosphamide 50 mg/kg, in 500 mL NS over 2 hours on days +3 and +4. Concomitant hydration with NS with 20 mEq/L at 250 mL/hr starting 4 hours before and continuing until 24 hours after the second dose is given. Furosemide on as needed basis to maintain fluid balance is also given. It is important to avoid administration of any immunosuppressive drugs include steroids after day 0.

Bortezomib 0.7 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3. intervention 2: Conditioning Regimen: Fludarabine 30 mg/m2 on days -7, -6, -5, -4, -3 and -2; Busulfan 0.8 mg/kg, every 6 hours on days -3 and -2; Patients with matched unrelated donor also receive rATG (Thymoglobulin ®) 2 mg/kg on days -4, -3, -2 and -1.

Cyclophosphamide 50 mg/kg, in 500 mL NS over 2 hours on days +3 and +4. Concomitant hydration with NS with 20 mEq/L at 250 mL/hr starting 4 hours before and continuing until 24 hours after the second dose is given. Furosemide on as needed basis to maintain fluid balance is also given. It is important to avoid administration of any immunosuppressive drugs include steroids after day 0.

Bortezomib 1 mg/ m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3. intervention 3: Conditioning Regimen: Fludarabine 30 mg/m2 on days -7, -6, -5, -4, -3 and -2; Busulfan 0.8 mg/kg, every 6 hours on days -3 and -2; Patients with matched unrelated donor also receive rATG (Thymoglobulin ®) 2 mg/kg on days -4, -3, -2 and -1.

Cyclophosphamide 50 mg/kg, in 500 mL NS over 2 hours on days +3 and +4. Concomitant hydration with NS with 20 mEq/L at 250 mL/hr starting 4 hours before and continuing until 24 hours after the second dose is given. Furosemide on as needed basis to maintain fluid balance is also given. It is important to avoid administration of any immunosuppressive drugs include steroids after day 0.

Bortezomib 1.3 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.

Protocol documents: