Clinical trial NCT01991301: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Graft-versus-host Disease
Keywords: graft-versus-host disease
stem cell transplantation
matched unrelated donors
proteosmoe inhibitor
carfilzumib
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2013-11-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: incidence of acute graft-versus host disease
timeFrame: 3 months
Secondary outcomes:
measure: incidence of chronic graft-versus-host disease
timeFrame: 1 year
measure: survival rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Tel-Hashomer
country: Israel
facility: Chaim Sheba Medical Center
Study officials:
affiliation: Chaim Sheba Medical Center
name: Arnon Nagler, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.