CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease

H. Lee Moffitt Cancer Center and Research Institute

Status and phase: Completed; Phase 1

Conditions: GVHD, Acute; GVHD; Graft-versus-host-disease

Treatments: Drug: Tacrolimus; Drug: BMS-986004; Drug: Sirolimus

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03605927

MCC-19305

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

Combination Therapy

Experimental group

Description:

BMS-986004: From day 13, intravenously (IV) every 2 week through day 100 post HCT. Tacrolimus: From day -3 as standard of care. Sirolimus: From day -1 as standard of care.

Treatment:

Drug: Sirolimus

Drug: BMS-986004

Drug: Tacrolimus