Carfilzomib for the Prevention of Graft Versus Host Disease

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

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 Overview

• Status: Unknown
• Conditions: Graft-versus-host Disease
• Intervention / Treatment: Drug: carfilzumib

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Tel-Hashomer, Israel, 52621
    • Recruiting
    • Chaim Sheba Medical Center
    • Contact: Avichai Shimoni, MD; Phone Number: 972 3 530 5830; Email: ashimoni@sheba.health.gov.il
    • Contact: Arnon Nagler, MD; Phone Number: 972 3 530 5830; Email: a.nagler@sheba.health.gov.il
    • Principal Investigator: Arnon Nagler, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with MDS/AML
2. 18 years or older and willing and able to comply with the protocol requirements.
3. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
4. Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
5. Patients conditioned with reduced intensity or reduced toxicity conditioning i.e. Fludarabine combine with Treosulfan or 2-4 days of I.V Busulfan.
6. Patients must sign written informed consent.
7. Adequate birth control in fertile patients.

Exclusion Criteria:

1. Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS.
2. Patients with respiratory failure (DLCO < 30%).
3. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
4. Patients with > grade II liver renal toxicity.
5. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate
6. Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
7. Creatinine > 2.0 mg/dl
8. ECOG-Performance status > 2
9. Uncontrolled infection
10. Pregnancy or lactation
11. CNS disease involvement
12. Pleural effusion or ascites > 1 liter.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: carfilzumib; carfilzumib will be added to the standard regimen of drugs for prevention of graft-versus-host disease.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sheba Medical Center

Publications and helpful links

General Publications

• Shimoni A, Shem-Tov N, Yerushalmi R, Danylesko I, Nagler A. Carfilzomib combined with cyclosporine and methotrexate for the prevention of graft-versus-host disease after allogeneic stem-cell transplantation from unrelated donors. Bone Marrow Transplant. 2021 Feb;56(2):451-456. doi: 10.1038/s41409-020-01044-5. Epub 2020 Sep 2.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): November 1, 2017
• Study Completion (Anticipated): November 1, 2017

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: November 18, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Estimate): December 2, 2015
• Last Update Submitted That Met QC Criteria: December 1, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: stem cell transplantation; graft-versus-host disease; matched unrelated donors; proteosmoe inhibitor; carfilzumib
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: SHEBA-12-9997-AN-CTIL