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Belumosudil for the Prevention of Graft-versus-Host Disease after Donor Hematopoietic Cell Transplant
Trial Status: active
This phase II trial tests the safety, side effects and effectiveness of belumosudil compared to a usual approach in reducing the risk of graft-versus-host disease (GVHD) in patients with a blood cancer who have had a donor (allogeneic) stem cell transplant. Stem cell transplants can cause GVHD, a condition that occurs when the healthy, blood-forming cells (stem cells) from the donor (the graft) attack the organs and tissues the body (the host), causing serious health problems. GVHD can affect the skin, liver, stomach, and intestines and may be mild or severe. In the most severe cases, GVHD can cause death. Belumosudil is a type of drug called a kinase inhibitor. Belumosudil targets and blocks a protein called rho-associated protein kinase 2 (ROCK2). By blocking this protein, belumosudil helps control the immune system and stops it from attacking the body after a transplant. By keeping the immune system under control, belumosudil may help prevent or manage the effects of GVHD. The usual approach for reducing the risk of GVHD is a calcineurin inhibitor (CNI) with or without post-transplant cyclophosphamide (PTCY). CNIs, such as tacrolimus, can weaken (suppress) the immune system to prevent the donor's immune cells from attacking the body. PTCY is in a class of medications called alkylating agents. It works by damaging the cell’s deoxyribonucleic acid and may kill cancer cells. It may also lower the body’s immune response. Giving belumosudil in combination with the usual approach may work better than the usual approach alone in reducing the risk of GVHD in patients with a blood cancer who have had an allogeneic stem cell transplant.
Inclusion Criteria
Patients ≥ 18 years-old at time of consent
Hematologic malignancy in morphologic remission who will be treated with reduced intensity (RI) or non-myeloablative (NMA) conditioning and GVHD prophylaxis CNI-based (CNI without PTCY) plus abatacept or PTCY-based (CNI with PTCY)
Recipients of 7-8/8 related or unrelated human leukocyte antigen (HLA)-matched or related haploidentical donor
Peripheral blood stem cell graft
Allo-HCT day ≤ 120 at time of consent
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): Patient has received an allo-HCT transplant and is in morphologic remission (blasts < 5%, no evidence of extramedullary disease in acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]). Patients with complete response (CR) with incomplete count recovery (CR with incomplete platelet recovery [CRp] or complete response with incomplete bone marrow recovery [CRi]) or minimal residual disease are allowed
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): Patient has achieved engraftment. Engraftment is defined as absolute neutrophil count (ANC) ≥ 500/µL and platelets ≥ 20000/µL on 3 consecutive measurements (each occurring at least 1 day apart). The patient must not have had a platelet transfusion within 7 days before the first measurement
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): Patient is ≥ 80 days and ≤ 120 days from allo-HCT infusion
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): Karnofsky score ≥ 70%
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): Total bilirubin ≤ 1.5 x ULN (unless benign congenital hyperbilirubinemia)
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m^2
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): Female subjects of childbearing potential (≤ 50 years old) have a negative serum or urine pregnancy test. Females of childbearing potential are defined as females without prior hysterectomy or who have had any evidence of menses in the past 12 months.
* Sexually active females of childbearing potential enrolled in the study must agree to consistently use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes:
** Intrauterine device (IUD) plus one barrier method
** Stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method
** 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gel that contain a chemical to kill sperm); or
** A vasectomized partner
POST-HCT (WITHIN 3 WEEKS BEFORE START OF BELUMOSUDIL TREATMENT): For male subjects who are sexually active and who are partners of females of childbearing potential: Agreement to use two forms of contraception as per above and to not donate sperm during the treatment period and for at least 3 months after the last dose of study drug
Exclusion Criteria
Recipient of CD34+ selected or engineered stem cell graft
Treatment with in vivo T cell depletion (e.g. anti-thymocyte globulin)
Evidence of current uncontrolled cardiovascular conditions, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
Pulmonary dysfunction with diffusion capacity of the lung for carbon monoxide (DLCO) < 50% corrected for hemoglobin
POST-HCT: Uncontrolled infection, including active hepatitis B and C. Definitive therapy for infection is required and must have no signs of progression within 7 days of the first day of study drug treatment
POST-HCT: Use of investigational agent within 14 days pre-HCT or anytime thereafter
POST-HCT: Active acute or chronic GVHD requiring systemic therapy (topical or local therapies are allowed)
POST-HCT: Active treatment with corticosteroids at a dose of ≥ 0.25 mg/kg/day for non-GVHD indication
POST-HCT: Uncontrolled psychosis, active suicidal ideation, or psychiatric hospitalization within the past year
POST-HCT: Female patient who is pregnant or breastfeeding
POST-HCT: Prior therapy with belumosudil
POST-HCT: Known allergy or sensitivity to belumosudil or any other ROCK2 inhibitor
Additional locations may be listed on ClinicalTrials.gov for NCT07006506.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-812-4017
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-812-4017
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-812-4017
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-812-4017
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-812-4017
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-812-4017
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-812-4017
PRIMARY OBJECTIVE:
I. To assess the efficacy of belumosudil in the improvement of GVHD/relapse-free survival (GRFS) at 1-year post-hematopoietic cell transplantation (HCT) for patients receiving PTCY GVHD prophylaxis and separately for patients receiving CNI-based (CNI without PTCY) plus abatacept GVHD prophylaxis.
SECONDARY OBJECTIVES:
I. The incidence of overall, grade 3-4 acute GVHD (aGVHD), and moderate/severe chronic GVHD (cGVHD).
II. The incidence of transplant-related mortality (TRM).
III. The incidence of malignant disease relapse.
IV. The probabilities of relapse-free survival (RFS) and overall survival (OS) at 1-year post HCT.
V. The proportion of participants with discontinuation of primary immunosuppressive medication after HCT.
VI. To describe the incidence and severity of serious adverse events.
EXPLORATORY OBJECTIVES:
I. Characteristics of immune reconstitution.
II. Describe the percentage of patients who get vaccines on time and the percentage of patients who do not respond to vaccines.
III. To assess bone health at 1-year post-HCT.
OUTLINE:
Patients undergo allogeneic (allo)-HCT and may receive tacrolimus with either cyclophosphamide and mycophenolate mofetil or with methotrexate or abatacept per standard of care. Starting on day 80 to 120 post-HCT, patients receive belumosudil orally (PO) once daily (QD) or twice daily (BID) for up to 1 year post-HCT in the absence of disease progression, unacceptable toxicity, or completion of tacrolimus. Patients also undergo dual x-ray absorptiometry (DXA) scan at 1 year post-HCT and bone marrow aspiration and biopsy, blood sample collection throughout the study. Additionally, patients may undergo computed tomography (CT) or positron emission tomography (PET)/CT throughout the study.
After completion of study treatment, patients are followed up at 28 days and at 56 days.
Trial PhasePhase II
Trial Typeprevention
Lead OrganizationMemorial Sloan Kettering Cancer Center
