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BMS-986004, Sirolimus, and Tacrolimus in Preventing Graft Versus Host Disease after Donor Stem Cell Transplant in Patients with Hematologic Cancer or Blood Disorder

Trial Status: Active

This phase I / II 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.

Inclusion Criteria

  • Hematologic malignancy or blood disorder requiring allogeneic HCT
  • Left ventricular ejection fraction (LVEF) >= 45% by multigated acquisition scan (MUGA) scan or echocardiography (ECHO)
  • Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and adjusted diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted values on pulmonary function tests
  • Transaminases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) < 2 times upper limit of normal values
  • Creatinine clearance >= 50 cc/min
  • Karnofsky performance status score (KPS) >= 80%
  • Patients must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched unrelated donor
  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • For females of reproductive potential: use of 2 methods of highly effective contraception
  • For males of reproductive potential: use of condoms

Exclusion Criteria

  • Active infection not controlled with appropriate antimicrobial therapy
  • Human immunodeficiency virus (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
  • Pregnancy or nursing
  • Known allergic reactions to components of the study agent
  • 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
  • Planned post transplant maintenance therapies such as FLT3 inhibitor, tyrosine kinase inhibitor, JAK inhibitors etc. are not allowed in phase 1 part B and Phase 2 portions of the trial

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Contact: Haris Ali
Phone: 626-256-4673

Florida

Tampa
Moffitt Cancer Center
Status: ACTIVE
Contact: Farhad Khimani
Phone: 813-745-7208

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE
Contact: Hannah Choe

PRIMARY OBJECTIVES:

I. Determine minimum biological effective dose of letolizumab (BMS–986004). (Phase I)

II. Determine safe total duration of drug exposure. (Phase I)

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 II)

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 phase II 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.

Trial Phase Phase I/II

Trial Type Prevention

Lead Organization
Moffitt Cancer Center

Principal Investigator
Farhad Khimani

  • Primary ID MCC-19305
  • Secondary IDs NCI-2019-00563
  • Clinicaltrials.gov ID NCT03605927