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Carfilzomib for the Prevention of Graft Versus Host Disease

Primary Purpose

Graft-versus-host Disease

Status

Unknown status

Phase

Phase 1

Locations

Israel

Study Type

Interventional

Intervention

carfilzumib

About this trial

This is an interventional treatment trial for Graft-versus-host Disease focused on measuring graft-versus-host disease, stem cell transplantation, matched unrelated donors, proteosmoe inhibitor, carfilzumib

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Chaim Sheba Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

carfilzumib

Arm Description

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.

Outcomes

Primary Outcome Measures

incidence of acute graft-versus host disease

We will evaluate the incidence of acute GVHD, grading and organ involvementBY STANDARD INTERNATIONAL CRITERIA.

Secondary Outcome Measures

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.

survival rate

We will evaluate overall and disease-free survival after stem cell transplantation

Full Information

NCT ID

NCT01991301

First Posted

November 18, 2013

Last Updated

December 1, 2015

Sponsor

Sheba Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01991301

Brief Title

Carfilzomib for the Prevention of Graft Versus Host Disease

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Unknown status

Study Start Date

November 2014 (undefined)

Primary Completion Date

November 2017 (Anticipated)

Study Completion Date

November 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sheba Medical Center

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft-versus-host Disease

Keywords

graft-versus-host disease, stem cell transplantation, matched unrelated donors, proteosmoe inhibitor, carfilzumib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

carfilzumib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

carfilzumib

Intervention Description

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

Primary Outcome Measure Information:

Title

incidence of acute graft-versus host disease

Description

We will evaluate the incidence of acute GVHD, grading and organ involvementBY STANDARD INTERNATIONAL CRITERIA.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

incidence of chronic graft-versus-host disease

Description

We will evaluate the progression of acute graft-versus-host disease to chronic graft-versus-host disease and the grading and organ involvement.

Time Frame

1 year

Title

survival rate

Description

We will evaluate overall and disease-free survival after stem cell transplantation

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Arnon Nagler, MD

Phone

972 3 530 5830

a.nagler@sheba.health.gov.il

First Name & Middle Initial & Last Name or Official Title & Degree

Avichai Shimoni, MD

Phone

972 3 530 5830

ashimoni@sheba.health.gov.il

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arnon Nagler, MD

Organizational Affiliation

Chaim Sheba Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chaim Sheba Medical Center

City

Tel-Hashomer

ZIP/Postal Code

52621

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Arnon Nagler, MD

Phone

972 3 530 5830

a.nagler@sheba.health.gov.il

First Name & Middle Initial & Last Name & Degree

Avichai Shimoni, MD

Phone

972 3 530 5830

ashimoni@sheba.health.gov.il

First Name & Middle Initial & Last Name & Degree

Arnon Nagler, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

32873915

Citation

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.

Results Reference

derived

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Carfilzomib for the Prevention of Graft Versus Host Disease

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