An official website of the United States government
A Study of Ruxolitinib for Preventing Graft-versus-Host Disease in People with a Hematologic Malignancy Who Will Receive a Stem Cell Transplant
Trial Status: active
This phase II trial compares the effect of ruxolitinib, an intermediate dose of post-transplant cyclophosphamide (PTCY), tacrolimus, and mycophenolate mofetil (MMF) to standard of care (SOC) treatment with full-dose PTCY, tacrolimus and MMF, on preventing graft-versus-host disease (GVHD) after a donor (allogeneic) hematopoietic stem cell transplantation (allo-HCT) in patients with a blood (hematologic) cancer. Allo-HCT is a procedure where healthy, blood-forming stem cells from a donor are infused into a patient and they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can attack the body's normal cells (called GVHD). PTCY is in a class of medications called alkylating agents. It works by damaging the cell’s deoxyribonucleic acid and may kill cancer cells. PTCY may prevent GVHD by targeting certain T cells (a type of white blood cell) that play a role in the immune system attack that causes GVHD. The use of full-dose PTCY is effective at preventing GVHD. However, it can cause side effects and a higher risk of infections. An intermediate dose (a non-standard approach) may decrease side effects and infections related to PTCY, but this slightly reduced dose may increase the risk of GVHD. Tacrolimus and MMF are in a class of medications called immunosuppressants. Both work by decreasing the activity of the immune system to prevent it from attacking the transplanted stem cells. Ruxolitinib, a tyrosine kinase inhibitor, blocks a protein called JAK, which may help keep abnormal blood cells or cancer cells from growing. It may also lower the body’s immune response and help prevent GVHD. Adding ruxolitinib to intermediate dose PTCY, tacrolimus and MMF may be an effective approach to prevent GVHD while reducing side effects and infection risk after an allo-HCT compared to SOC treatment with full-dose PTCY, tacrolimus and MMF in patients with a hematologic cancer.
Inclusion Criteria
Patients ≥ 18- years-old at time of consent
Diagnosis: Hematologic malignancy in morphologic remission (blasts < 5%, no evidence of extramedullary disease in acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]). Patients with complete remission (CR) with incomplete count recovery (CR with incomplete platelet recovery [CRp] or CR with incomplete hematologic recovery [CRi]) or minimal residual disease are allowed
* Patients with lymphoma must have a complete or partial response
Donor: Related or unrelated 7-8/8 human leukocyte antigen (HLA)-matched or related haploidentical
Karnofsky score ≥ 70%
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 the 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
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)
Severely impaired renal function defined by serum creatinine > 2mg/dL, renal dialysis requirement
Use of investigational agent within 14 days pre-HCT
Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
Uncontrolled psychiatric illness
Female patient who is pregnant or breastfeeding
Known allergy or sensitivity to ruxolitinib
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07359859.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-608-3739
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-608-3739
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-608-3739
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-608-3739
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-608-3739
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-608-3739
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Doris Mariela Ponce
Phone: 646-608-3739
PRIMARY OBJECTIVE:
I. To assess the chronic GVHD (cGVHD)-free survival within treatment arm intermediate dose PTCY/tacrolimus/MMF/ruxolitinib and full dose PTCY/tacrolimus/MMF at 1-year post-HCT.
SECONDARY OBJECTIVES:
I. The incidence of grade 2-4 infections.
II. The incidence of overall, grade 3-4 acute GVHD (aGVHD), and moderate/severe cGVHD.
III. The incidence of transplant-related mortality (TRM).
IV. The incidence of malignant disease relapse or progression.
V. The probabilities of progression-free survival (PFS) and overall survival (OS) at 1-year post-HCT.
VI. The probability of cGVHD relapse-free survival (CRFS) at 1-year post-HCT.
VII. The proportion of participants with discontinuation of primary immunosuppressive medication before 1-year post-HCT.
VIII. To describe the incidence and severity of serious adverse events.
EXPLORATORY OBJECTIVES:
I. Characteristics of immune reconstitution per treatment arm.
II. Describe the percentage of patients who get vaccines on time and the percentage of patients who do not respond to vaccines per treatment arm.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients undergo SOC allo-HCT on day 0, full-dose PTCY intravenously (IV) over 1-2 hours on days 3 and 4 and MMF IV over 2 hours or orally (PO) thrice daily (TID) on days 5-35. Starting on day 5, patients receive tacrolimus PO or IV once daily (QD) and continues until tapered per SOC.
ARM II: Patients undergo SOC allo-HCT on day 0, intermediate dose PTCY IV over 1-2 hours on days 3 and 4 and MMF IV over 2 hours or PO TID on days 5-35. Starting on day 5, patients receive tacrolimus PO or IV QD up to SOC tapering within 2 weeks of starting ruxolitinib. Starting 60-120 days post-HCT, patients receive ruxolitinib PO twice daily (BID) for up to 1 year post-HCT in the absence of disease progression, development of acute or chronic GVHD or unacceptable toxicity.
Patients also undergo blood sample collection and bone marrow aspiration and biopsy throughout the study. Additionally, patients may undergo positron emission tomography (PET)/computed tomography (CT) throughout the study.
After completion of study treatment, patients who receive ruxolitinib are followed up at 4-8 weeks. Patients who did not receive ruxolitinib are followed up at 1 year post-HCT.
Trial PhasePhase II
Trial Typeprevention
Lead OrganizationMemorial Sloan Kettering Cancer Center
