Recruiting
Phase 3

Tacrolimus & Ruxolitinib vs. Post-Transplant Cyclophosphamide

Sponsor:

Incyte Corporation

Code:

NCT06615050

Conditions

Graft-versus-host Disease (GVHD)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Tacrolimus (Tac)

Methotrexate (MTX)

Ruxolitinib (Rux)

Cyclophosphamide

Mycophenolate mofetil (MMF)

Study Details

Brief summary:

The purpose of this study is to assess Tacrolimus/Methotrexate/Ruxolitinib versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation

Conditions

Graft-versus-host Disease (GVHD)

Study ID

NCT06615050

Start date

Apr 2, 2025

Status verified date

May, 2026

Completion date

Jan 17, 2031

Anticipated

Primary completion date

Jan 17, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age 18.0 years or older at the time of enrollment.
  • Participants undergoing allogeneic HCT for one of the following indications:

  • Acute leukemia or chronic myelogenous leukemia with no circulating blasts and with less than 5% blasts in the bone marrow. Therapy related myeloid neoplasms are allowed.
  • Myelodysplasia/chronic myelomonocytic leukemia with no circulating blasts and with less than 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with < 5% versus 5-10% blasts in this disease). Therapy related myeloid neoplasms are allowed.
  • Lymphoma \[follicular lymphoma, Hodgkin lymphoma, diffuse large B cell lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma\].
  • Planned NMA/reduced intensity conditioning regimen.
  • Participants must have a related or unrelated PBSC donor as follows:

  • Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. HLA-matched parents and children may be used as donors.
  • Unrelated donor must be a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and meet NMDP criteria for donation.
  • Donor selection must comply with 21 CFR 1271.
  • Cardiac function: Left ventricular ejection fraction at least 45%.
  • Estimated glomerular filtration rate greater than 60 ml/min/1.73 m2 using the 2021 CKD-EPI formula Note: For eligibility, GFR by 2021 CKD-EPI is required. A baseline creatinine clearance by Cockcroft-Gault should be done to establish baseline CrCl for ruxolitinib dosing.
  • Pulmonary function: DLCO corrected for hemoglobin at least 40% and FEV1 predicted at least 50%.
  • Liver function: AST/ALT < 3x ULN; Total bilirubin < 2 mg/dL excluding Gilbert's syndrome or hemolysis.
  • Karnofsky Performance Score of at least 60%.
  • Female participants (unless postmenopausal for at least one year before the screening visit, or surgically sterilized), agree to practice two effective methods of contraception at the same time, or agree to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 15 months post-transplant. Fertility preservation methods will be left to institutional standards.
  • Male participants (even if surgically sterilized), of partners of women of childbearing potential must agree to one of the following: practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 15 months post-transplant.
  • Plans for the use of targeted small molecule inhibitor post-transplant maintenance therapy must be disclosed upon enrollment and must be used irrespective of the outcome of the randomization. Planned use of investigational maintenance agents is not permitted. Planned hypomethylating agents as maintenance therapy is not permitted.
  • Voluntary written consent obtained prior to the performance of any study-related procedure that is not a part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

Exclusion Criteria:

  • Prior allogeneic transplant.
  • Active CNS involvement by malignant cells.
  • Participants with secondary AML arising from myeloproliferative neoplasms or secondary AML arising from overlap syndromes, including CMML and MDS/MPN syndromes; participants with secondary AML arising from myelodysplastic neoplasm are eligible.
  • Participants with primary, post-Essential Thrombocythemia (post-ET) and post-Polycythemia Vera (post-PV) myelofibrosis.
  • Participants with uncontrolled bacterial, viral, or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
  • Active or inadequately treated latent infection with Mycobacterium tuberculosis (i.e., TB).
  • Presence of clinically significant fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated.
  • Participants seropositive for human immunodeficiency virus (HIV) with detectable viral load. HIV+ participants with an undetectable viral load on antiviral therapy are eligible.
  • Evidence of uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV). The study allows:

  • Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis to prevent potential HBV reactivation.
  • Positive HCV serology with quantitative PCR for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment.
  • Arterial or venous thrombosis including DVT, PE, stroke, and myocardial infarction within six (6) months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia. Catheter-associated DVT is not exclusionary.
  • Female participants who are pregnant (as per institutional practice) or lactating.
  • Participants with a serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Participants with prior malignancies except resected non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent < 5 years previously must be reviewed and approved by the Protocol Officer or Chairs.
  • Planned use of ATG or alemtuzumab in conditioning regimen.
  • Planned use of prophylactic donor leukocyte infusions.
  • Prior use of ruxolitinib.
  • Prior use of immune checkpoint inhibitors (i.e., PD1, PDL1, CTLA4 modulators) within six (6) months prior to conditioning.
  • For participants with 7/8 HLA-matched donors:

  • Donor specific antibodies (DSAs) directed at the mismatched donor allele.
  • Any use of desensitization protocols.
  • Treatment with any other Investigational Medicinal Product (IMP) is not allowed while on study treatment. An IMP is defined as medications without any known FDA or EMA approved indications.

Study Design

Enrollment

572 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Finding Run-In Group 1: Tac/MTX/Ruxolitnib Dose 1

Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses.

experimental: Dose Finding Run-In Group 2: Tac/MTX/Ruxolitnib Dose 2

Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses.

experimental: Main Study Group A: Tac/MTX/Ruxolitnib

Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses.

active comparator: Main Study Group B: PTCy/Tac/MMF

Post-transplant cyclophosphamide/ tacrolimus/ mycophenolate mofetil (PTCy/Tac/MMF) at the protocol defined doses.

Interventions

Tacrolimus (Tac)

Tablet or intravenously (IV)

Methotrexate (MTX)

Intravenously (IV)

Ruxolitinib (Rux)

Tablet

Cyclophosphamide

Intravenously (IV)

Mycophenolate mofetil (MMF)

Tablet or intravenously (IV)

Primary outcome measure

  • GVHD-free survival (GFS) [ Time Frame: Up to 24 months post-transplant (Day 0) ]

Central Contacts and Locations

Central contacts

Incyte Corporation Call Center (US)

1.855.463.3463medinfo@incyte.com

Incyte Corporation Call Center (ex-US)

+800 00027423eumedinfo@incyte.com

Locations

Stanford Cancer Center

Recruiting

Palo Alto, California, United States, 94304

University of California San Francisco

Recruiting

San Francisco, California, United States, 94158

University of Miami

Recruiting

Miami, Florida, United States, 33136

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Blood and Marrow Transplant Group of Georgia

Recruiting

Atlanta, Georgia, United States, 30342

Indiana University Cancer Center

Recruiting

Indianapolis, Indiana, United States, 46202

University of Kansas Hospital Authority

Recruiting

Kansas City, Kansas, United States, 66160

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Karmanos Cancer Institute

Recruiting

Detroit, Michigan, United States, 48201

Henry Ford Hospital

Recruiting

Detroit, Michigan, United States, 48202

Washington University

Recruiting

St Louis, Missouri, United States, 63110

Mount Sinai Hospital

Recruiting

New York, New York, United States, 10029

Memorial Sloan Kettering

Recruiting

New York, New York, United States, 10065

University of North Carolina At Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27514

Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28204

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27705

Cleveland Clinic

Recruiting

Cleveland, Ohio, United States, 44195

Ohio State University

Recruiting

Columbus, Ohio, United States, 43210

Oregon Health & Science University

Recruiting

Portland, Oregon, United States, 97239

University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Sarah Cannon

Recruiting

Nashville, Tennessee, United States, 37203

Vanderbilt Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Baylor College of Medicine

Recruiting

Houston, Texas, United States, 77030

Virginia Commonwealth University, North Hospital

Recruiting

Richmond, Virginia, United States, 23298

Fred Hutchinson Cancer Research Center

Recruiting

Seattle, Washington, United States, 98109

University of Wisconsin

Recruiting

Madison, Wisconsin, United States, 53705

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

More Information

Sponsor

Incyte Corporation

Last update posted

May 20, 2026

Last verified

May, 2026

Keywords

  • Graft-versus-host Disease (GVHD)
  • Chronic GvHD (cGvHD)
  • steroid-refractory
  • ruxolitinib
  • Janus kinase inhibitor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-02. This information was provided to ClinicalTrials.gov by Incyte Corporation on 2026-05-20. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.