BMS-986004, Sirolimus, and Tacrolimus in Preventing Graft Versus Host Disease after Donor Stem Cell Transplant in Patients with Hematologic Cancer or Blood Disorder
- 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
- 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
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)
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
Moffitt Cancer Center
- Primary ID MCC-19305
- Secondary IDs NCI-2019-00563
- Clinicaltrials.gov ID NCT03605927