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

NCT ID: NCT03605927

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-15
• Study Completion Date: 2023-07-25

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Combination Therapy

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.

Group Type: EXPERIMENTAL

BMS-986004

Intervention Type: DRUG

BMS-986004 will be administered in ascending dose cohorts in the phase I component of the trial. Based on prior PK and PD data, dose levels of 225 mg, 675 mg, and 1500 mg (3 total phase I dose levels) will be examined. BMS-986004 will be given intravenously (IV) every 2 weeks, starting from day -3 (i.e., three days prior to HCT) onward through a total of 100 days post-HCT. The maximum tolerated dose (MTD) identified in the phase I component of the trial will be carried forward as the recommended dose level in the phase 1 expansion cohort.

Sirolimus

Intervention Type: DRUG

Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards.

Sirolimus (SIR) will be given as a loading dose on day -1 orally, then daily as maintenance therapy with target levels of 10-14ng/mL early post-HCT, then tapered to 5-14ng/mL range.

Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions.

Tacrolimus

Intervention Type: DRUG

Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards.

In brief, tacrolimus (TAC) will be started on day -3 IV, and transitioned to oral TAC when oral medications are tolerated; target level is 3-7ng/mL.

Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions.

Interventions

BMS-986004

BMS-986004 will be administered in ascending dose cohorts in the phase I component of the trial. Based on prior PK and PD data, dose levels of 225 mg, 675 mg, and 1500 mg (3 total phase I dose levels) will be examined. BMS-986004 will be given intravenously (IV) every 2 weeks, starting from day -3 (i.e., three days prior to HCT) onward through a total of 100 days post-HCT. The maximum tolerated dose (MTD) identified in the phase I component of the trial will be carried forward as the recommended dose level in the phase 1 expansion cohort.

Intervention Type: DRUG

Sirolimus

Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards.

Sirolimus (SIR) will be given as a loading dose on day -1 orally, then daily as maintenance therapy with target levels of 10-14ng/mL early post-HCT, then tapered to 5-14ng/mL range.

Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions.

Intervention Type: DRUG

Tacrolimus

Sirolimus and tacrolimus (standard of care pharmacologic immune suppression) will be given according to institutional standards.

In brief, tacrolimus (TAC) will be started on day -3 IV, and transitioned to oral TAC when oral medications are tolerated; target level is 3-7ng/mL.

Program standards will be used for SIR and TAC level monitoring frequency and dose adjustments, including careful attention to drug-interactions.

Intervention Type: DRUG

Other Intervention Names

Anti-CD40L Domain Antibody; Standard of Care; SIR; Standard of Care; TAC

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Farhad Khimani, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

City of Hope Cancer Center

Duarte, California, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

Related Links

https://www.moffitt.org/clinical-trials-research/clinical-trials/

Moffitt Cancer Center Clinical Trials website

Other Identifiers

MCC-19305

Identifier Type: -

Identifier Source: org_study_id