A Study of Ruxolitinib for Preventing Graft-Versus-Host Disease in People With a Hematologic Malignancy Who Will Receive a Stem Cell Transplant

Randomized Pilot Study of Ruxolitinib for Switch-Maintenance Prophylaxis of Graft-versus-Host Disease in Allogeneic Hematopoietic Cell Transplantation After Intermediate-Dose Post-Transplant Cyclophosphamide (Rux Switch-Maintenance in Intermediate PTCY: RuSMa-PTCY) in Comparison to Full-Dose PTCY

The researchers are doing this study to compare 2 different GVHD prevention (prophylaxis) approaches. The researchers will see which approach is good or more effective at preventing chronic GVHD until 1 year after allogeneic hematopoietic stem cell transplantation (allo-HCT).

Study Overview

• Status: Recruiting
• Conditions: Hematologic Malignancies
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Cyclophosphamide; Drug: Mycophenolate Mofetil; Drug: Ruxolitinib; Drug: Tacrolimus; Drug: Tacrolimus

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Doris Ponce, MD, MS; Phone Number: 646-608-3739; Email: BMTTrials@mskcc.org
• Study Contact Backup: Name: Brian Shaffer, MD; Phone Number: 646-608-3737

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
      • Contact: Doris Ponce, MD; Phone Number: 646-608-3739
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Doris Ponce, MD; Phone Number: 646-608-3739
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Doris Ponce, MD; Phone Number: 646-608-3739
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)
      • Contact: Doris Ponce, MD; Phone Number: 646-608-3739
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Doris Ponce, MD; Phone Number: 646-608-3739
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Doris Ponce, MD; Phone Number: 646-608-3739
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited protocol activites)
      • Contact: Doris Ponce, MD; Phone Number: 646-608-3739

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥18- years-old at time of consent
• Diagnosis: hematologic malignancy in morphologic remission (blasts <5%, no evidence of extramedullary disease in AML or MDS). Patients with CR with incomplete count recovery (CRp or CRi) or minimal residual disease are allowed. Patients with lymphoma must have a complete or partial response
• Donor: related or unrelated 7-8/8 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)
• Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: An intermediate dose (medium dose) of PTCY, tacrolimus, MMF, and the drug ruxolitinib; will receive an intermediate (medium) dose of PTCY, tacrolimus, MMF,and ruxolitinib	Drug: Cyclophosphamide; An intermediate dose (medium dose) of Post-transplant Cyclophosphamide; Drug: Cyclophosphamide; A full dose of Post-transplant Cyclophosphamide; Drug: Mycophenolate Mofetil; Day +5 to +35; Other Names: MMF; Drug: Ruxolitinib; twice a day; Drug: Tacrolimus; Day +5, taper per SoC; Drug: Tacrolimus; Day +5, taper initiation within 2 weeks of starting Ruxolitinib
Active Comparator: A full dose of PTCY, tacrolimus, and MMF (the standard GVHD prevention approach); will receive a full dose of PTCY, tacrolimus, and MMF (the standard GVHD prevention approach)	Drug: Cyclophosphamide; An intermediate dose (medium dose) of Post-transplant Cyclophosphamide; Drug: Cyclophosphamide; A full dose of Post-transplant Cyclophosphamide; Drug: Mycophenolate Mofetil; Day +5 to +35; Other Names: MMF; Drug: Tacrolimus; Day +5, taper per SoC; Drug: Tacrolimus; Day +5, taper initiation within 2 weeks of starting Ruxolitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
assess cGVHD-free survival	Chronic GVHD-free survival is defined as moderate-to-severe cGVHD requiring systemic immunosuppression treatment from the date of allo-HCT to first occurrence with follow-up through 12 months post-HCT or death.	1 year post-HCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of grade 2-4 infections.	Grade 2-4 infections by CTCAE v5 either clinically or microbiologically will be assessed throughout the study until day +365. Causality and relationship with ruxolitinib will be determined.	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: Doris Ponce, MD, MS, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 21, 2026
• First Submitted That Met QC Criteria: January 21, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: graft-versus-host disease (GVHD); allogeneic hematopoietic stem cell transplant (allo-HCT)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Immune System Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Graft vs Host Disease; Organic Chemicals; Fatty Acids; Lipids; Hydrocarbons; Acids, Acyclic; Carboxylic Acids; Macrolides; Lactones; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Caproates; Cyclophosphamide; Mycophenolic Acid; Tacrolimus; ruxolitinib
• Other Study ID Numbers: 25-212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No