This phase I trial studies the side effects, best dose and how well BMS-986004 works when given together with sirolimus and tacrolimus in preventing graft versus host disease after donor stem cell transplant in patients with hematologic cancer or blood disorder. Immunosuppressive therapy, such as BMS-986004, sirolimus, and tacrolimus, are used to decrease the body’s immune response and may help reduce the incidence of graft versus host disease.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03605927.
PRIMARY OBJECTIVES:
I. Determine minimum biological effective dose of letolizumab (BMS–986004). (Phase I Dose Escalation)
II. Determine safe total duration of drug exposure. (Phase I Dose Escalation)
III. Determine if anti-CD40L domain antibody therapy in combination with standard sirolimus-tacrolimus immune suppression prophylaxis significantly reduces the cumulative incidence of grade II-IV acute graft‐versus‐host disease (GVHD) after hematopoietic cell transplantation (HCT). (Phase I Dose Expansion)
SECONDARY OBJECTIVES:
I. Determine if anti-CD40L domain antibody therapy will promote development of donor-recipient immune tolerance, as measured by reduced incidence of chronic GVHD, and successful liberation from immune suppression after HCT.
II. Examine safety of anti-CD40L domain antibody therapy, as measured by comprehensive study of toxicity and mortality outcomes after HCT.
III. Investigate how anti-CD40L domain antibody therapy impacts markers of immune activation.
OUTLINE: This is a phase I, dose-escalation study of letolizumab followed by a dose-expansion study. Patients are assigned to 1 of 2 groups.
GROUP I: Beginning day -3 before transplant, patients receive letolizumab intravenously (IV) over 120 minutes every 2 weeks for up to 7 doses in the absence of disease progression or unacceptable toxicity. Patients also receive standard tacrolimus IV transitioned to orally (PO) beginning on day -3 and standard sirolimus PO daily beginning on day -1 in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients also receive standard tacrolimus IV transitioned to PO beginning on day -3 and standard sirolimus PO daily beginning on day -1 in the absence of disease progression or unacceptable toxicity.
Lead OrganizationMoffitt Cancer Center
Principal InvestigatorFarhad Khimani
