Clinical trial NCT03605927: CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease
Official title: CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Graft-versus-host-disease
GVHD
GVHD, Acute
Keywords: HCT
hematopoietic cell transplantation
antibody therapy
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-07-30
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to examine the safety and efficacy of the addition of BMS-986004 to standard of care Sirolimus (SIR)-based immune suppression.

Detailed description: The approach builds upon extensive evidence supporting the benefit of CD40L blockade in disrupting key signaling events associated with immune activation. The trial addresses a pressing clinical need, namely prevention of Graft-Versus-Host Disease (GVHD) after hematopoietic cell transplantation (HCT) and promotion of donor-recipient immune tolerance. The safety profile of this anti-CD40L antibody overcomes major prior limitations, and the planned biologic studies will provide significant mechanistic insight.

Eligibility criteria: Inclusion Criteria:

* Hematologic malignancy or blood disorder requiring allogeneic HCT
* Adequate vital organ function as defined per protocol
* Karnofsky Performance Status Score (KPS) ≥ 80%
* Participants must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched-related or unrelated donor

Exclusion Criteria:

* Active infection not controlled with appropriate antimicrobial therapy
* HIV, hepatitis B or C infection or known history of HIV, hepatitis B or C(all patients will be tested for HIV, hepatitis B and C as part of standard pre-transplant testing, and will be excluded from this trial if positive)
* Anti-thymocyte globulin, or cyclophosphamide administered within 14 days before or planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days after HCT
* Known allergic reactions to components of the study drug
* Concurrent treatment with another investigational drug
* History of thromboembolism, transient ischemic attack, stroke, myocardial infarction within 3 months preceding the transplant, or uncontrolled congestive heart failure or cardiac arrhythmias.
* Post-transplant maintenance therapies such as FLT3 inhibitor, tyrosine kinase inhibitor, JAK inhibitors etc. are not allowed if plan is to initiate such therapies \<90 days post-transplant. Patient will be eligible if plan to initiate maintenance therapy is after day 90 post-transplant.

Primary outcomes:
measure: Incidence of Grade II-IV Acute Graft-versus Host Disease
timeFrame: 1 year post HCT
Secondary outcomes:
measure: Chronic Graft-versus Host Disease Through 1 Year Post HCT
timeFrame: 1 year post HCT
measure: Malignancy Relapse Post-HCT
timeFrame: 1 year post HCT
measure: Non-relapse Mortality
timeFrame: 1 year post HCT
measure: Overall Survival (OS)
timeFrame: 1 year post HCT
Other outcomes:
measure: Glucocorticoid Exposure
timeFrame: 1 year post HCT
measure: Neutrophil and Platelet Engraftment
timeFrame: 1 year post HCT
Locations:
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Farhad Khimani, M.D.
role: PRINCIPAL_INVESTIGATOR
References: