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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combination Therapy | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BMS-986004 | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Grade II-IV Acute Graft-versus Host Disease | Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) by day 100 after hematopoietic cell transplantation (HCT). Acute GVHD severity will be determined by standard Consensus Criteria, and the cumulative incidence of grade II-IV acute GVHD will be reported through day 100 post-HCT, with relapse and death as competing risk events. | 1 year post HCT |
| Measure | Description | Time Frame |
|---|---|---|
| Chronic Graft-versus Host Disease Through 1 Year Post HCT | NIH criteria defined chronic graft-versus-host disease through 1 year post-HCT. Chronic GVHD will be defined by the presence of chronic GVHD defining features, regardless of time post-HCT, in keeping with the NIH Consensus Criteria on diagnosis and staging of chronic GVHD. Individual affected organs are staged on 0-3 severity scale, and summarized for an overall global severity score. The presence of acute GVHD features defines the following subgroups: (1) late acute GVHD (sole presence of acute GVHD features after day 100 post-HCT), (2) overlap subtype of chronic GVHD (co-occurrence of chronic and acute GVHD features, and (3) classic chronic GVHD (absence of concurrent acute GVHD features). |
| Measure | Description | Time Frame |
|---|---|---|
| Glucocorticoid Exposure | Systemic steroid (prednisone or equivalent) dose per kg of recipient body weight will be collected at each study visit, and overall exposure determined. | 1 year post HCT |
| Neutrophil and Platelet Engraftment |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Farhad Khimani, M.D. | H. Lee Moffitt Cancer Center and Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope Cancer Center | Duarte | California | 91010 | United States | ||
| H. Lee Moffitt Cancer Center and Research Institute |
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| Label | URL |
|---|---|
| Moffitt Cancer Center Clinical Trials website | View source |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D020123 | Sirolimus |
| D059039 | Standard of Care |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D019984 | Quality Indicators, Health Care |
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| Sirolimus | 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. |
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| Tacrolimus | 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. |
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| 1 year post HCT |
| Malignancy Relapse Post-HCT | Defined as hematologic relapse or any unplanned intervention (including withdrawal of immune suppression) to prevent progression of disease in patients with evidence (molecular, cytogenetic, flow cytometric, radiographic) of malignant disease after HCT. | 1 year post HCT |
| Non-relapse Mortality | Defined as death in the absence of malignancy relapse post-HCT. | 1 year post HCT |
| Overall Survival (OS) | Defined as time from HCT to death or censoring for last follow up. | 1 year post HCT |
Stable engraftment is defined as a sustained absolute neutrophil count > 500 over 3 days, as well as a sustained platelet count of > 20 over 7 days without transfusion support. Time to engraftment is defined as time from day 0 to day of sustained engraftment per above criteria.
| 1 year post HCT |
| Tampa |
| Florida |
| 33612 |
| United States |
| Ohio State University Comprehensive Cancer Center | Columbus | Ohio | 43210 | United States |
| D011787 |
| Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |