The Safety and Efficacy of Carfilzomib -a Novel Proteasome Inhibitor- for the Prevention of Acute Graft Versus Host Disease
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Sheba Medical Center
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- incidence of acute graft-versus host disease
Study Overview
Brief Summary
The aim of this study is to evaluate the safety and efficacy of Carfilzumib, which is a novel biological agent used in the treatment of multiple myeloma in preventing graft-versus-host disease, after stem cells transplantation from unrelated donors.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with MDS/AML
- •18 years or older and willing and able to comply with the protocol requirements.
- •LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
- •Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
- •Patients conditioned with reduced intensity or reduced toxicity conditioning i.e. Fludarabine combine with Treosulfan or 2-4 days of I.V Busulfan.
- •Patients must sign written informed consent.
- •Adequate birth control in fertile patients.
Exclusion Criteria
- •Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS.
- •Patients with respiratory failure (DLCO < 30%).
- •Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
- •Patients with > grade II liver renal toxicity.
- •Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate
- •Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
- •Creatinine > 2.0 mg/dl
- •ECOG-Performance status > 2
- •Uncontrolled infection
- •Pregnancy or lactation
- •CNS disease involvement
- •Pleural effusion or ascites > 1 liter.
Arms & Interventions
carfilzumib
Carfilzomib at a dose of 20mg/m2 I.V. will be administrated at day 1, 2 post infusion of the stem cell (SC) graft to the first 10 patients. If no > grade II toxicity* the next 10 patients will receive Carfilzomib (27 mg/m2) at day 1,2 and 8, 9, 15 and 16. If no > grade II toxicity* the next 10 patients will receive 2-3 cycles of Carfilzomib (27 mg/m2) administered at day 1,2 8,9,15 and 16 post SC graft infusion.
Intervention: carfilzumib (Drug)
Outcomes
Primary Outcomes
incidence of acute graft-versus host disease
Time Frame: 3 months
We will evaluate the incidence of acute GVHD, grading and organ involvementBY STANDARD INTERNATIONAL CRITERIA.
Secondary Outcomes
- incidence of chronic graft-versus-host disease(1 year)
- survival rate(2 years)