Carfilzomib for the Prevention of Graft Versus Host Disease

Study Overview
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Brief Summary
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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.

Official Title
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The Safety and Efficacy of Carfilzomib -a Novel Proteasome Inhibitor- for the Prevention of Acute Graft Versus Host Disease

Conditions
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Graft-versus-host Disease

Intervention / Treatment
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* Drug: carfilzumib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carfilzumib<br>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. | Drug: carfilzumib<br>* carfilzumib will be added to the standard regimen of drugs for prevention of graft-versus-host disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of acute graft-versus host disease | We will evaluate the incidence of acute GVHD, grading and organ involvementBY STANDARD INTERNATIONAL CRITERIA. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of chronic graft-versus-host disease | We will evaluate the progression of acute graft-versus-host disease to chronic graft-versus-host disease and the grading and organ involvement. | 1 year | 
| survival rate | We will evaluate overall and disease-free survival after stem cell transplantation | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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graft-versus-host disease, stem cell transplantation, matched unrelated donors, proteosmoe inhibitor, carfilzumib