Graft-versus-host Disease (GVHD)Phase 3NCT06615050
A Study of Tacrolimus/Methotrexate/Ruxolitinib Versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation (BMT CTN 2203)
A Phase 3 study testing Tacrolimus (Tac), Methotrexate (MTX) and Ruxolitinib (Rux) in people with Graft-versus-host Disease (GVHD), run by Incyte Corporation at 30 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-versus-host Disease (GVHD)
- What is being tested?
- Tacrolimus (Tac), Methotrexate (MTX) and Ruxolitinib (Rux)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 572 participants
- Where
- 30 sitesUnited States
- Study dates
- 2 Apr 2025to 17 Jan 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
30 sites in 1 country. Contact the study team or a site near you to ask about taking part.
30 sites in 1 country
United States30 sites, 30 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
- Recruiting
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
University of North Carolina At Chapel Hill
Chapel Hill, North Carolina, 27514
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
- Recruiting
Levine Cancer Institute
Charlotte, North Carolina, 28204
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Recruiting
Ohio State University
Columbus, Ohio, 43210
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
- Recruiting
Henry Ford Hospital
Detroit, Michigan, 48202
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27705
- Recruiting
Baylor College of Medicine
Houston, Texas, 77030
- Recruiting
Indiana University Cancer Center
Indianapolis, Indiana, 46202
- Recruiting
University of Kansas Hospital Authority
Kansas City, Kansas, 66160
- Recruiting
University of Wisconsin
Madison, Wisconsin, 53705
- Recruiting
University of Miami
Miami, Florida, 33136
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Recruiting
Sarah Cannon
Nashville, Tennessee, 37203
- Recruiting
Vanderbilt Medical Center
Nashville, Tennessee, 37232
- Recruiting
Mount Sinai Hospital
New York, New York, 10029
- Recruiting
Memorial Sloan Kettering
New York, New York, 10065
- Recruiting
Stanford Cancer Center
Palo Alto, California, 94304
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
- Recruiting
Oregon Health & Science University
Portland, Oregon, 97239
- Recruiting
Virginia Commonwealth University, North Hospital
Richmond, Virginia, 23298
- Recruiting
University of California San Francisco
San Francisco, California, 94158
- Recruiting
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
- Recruiting
Washington University
St Louis, Missouri, 63110
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Randomized, Multicenter, Phase III Trial of Tacrolimus/Methotrexate/Ruxolitinib Versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation
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)
- Being tested
- Tacrolimus (Tac), Methotrexate (MTX), Ruxolitinib (Rux), Cyclophosphamide, Mycophenolate mofetil (MMF)
- Keywords
- Graft-versus-host Disease (GVHD), Chronic GvHD (cGvHD), steroid-refractory, ruxolitinib, Janus kinase inhibitor
- Medical subject headings
- Graft vs Host Disease, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus (Tac)Drug
Tablet or intravenously (IV)
Methotrexate (MTX)Drug
Intravenously (IV)
Ruxolitinib (Rux)Drug
Also called Jakafi, INCB018424
Tablet
CyclophosphamideDrug
Intravenously (IV)
Mycophenolate mofetil (MMF)Drug
Tablet or intravenously (IV)
| Study group | Role | What they receive |
|---|---|---|
| Dose Finding Run-In Group 1: Tac/MTX/Ruxolitnib Dose 1 | Experimental | Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses. Receives: Drug: Tacrolimus (Tac); Drug: Methotrexate (MTX); Drug: Ruxolitinib (Rux) |
| Dose Finding Run-In Group 2: Tac/MTX/Ruxolitnib Dose 2 | Experimental | Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses. Receives: Drug: Tacrolimus (Tac); Drug: Methotrexate (MTX); Drug: Ruxolitinib (Rux) |
| Main Study Group A: Tac/MTX/Ruxolitnib | Experimental | Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses. Receives: Drug: Tacrolimus (Tac); Drug: Methotrexate (MTX); Drug: Ruxolitinib (Rux) |
| Main Study Group B: PTCy/Tac/MMF | Active comparator | Post-transplant cyclophosphamide/ tacrolimus/ mycophenolate mofetil (PTCy/Tac/MMF) at the protocol defined doses. Receives: Drug: Tacrolimus (Tac); Drug: Cyclophosphamide; Drug: Mycophenolate mofetil (MMF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
GVHD-free survival (GFS)
GFS will be defined as the elapsed time between the date of transplant to Grade III-IV acute graft-versus host disease (GVHD), chronic GVHD requiring systemic immune suppression, or death by any cause.
Measured: Up to 24 months post-transplant (Day 0)
Secondary outcomes (20)
GVHD/relapse or Progression-free Survival (GRFS)
Defined as Grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, underlying disease relapse or progression, or death by any cause.
Measured: Up to 24 months post-transplant (Day 0)
Incidence of chronic GVHD
Defined by the protocol.
Measured: Up to 24 months post-transplant (Day 0)
Incidence of acute grade 2-4 and 3-4 graft versus host disease (GVHD)
Defined by the protocol.
Measured: Up to 24 months post-transplant (Day 0)
Time to neutrophil and platelet recovery
Defined by the Protocol.
Measured: Up to 24 months post-transplant (Day 0)
Donor Cell Engraftment
Defined by the protocol.
Measured: Up to 24 months post-transplant (Day 0)
Cumulative incidence of primary and secondary graft failure
Primary graft failure is defined as no neutrophil recovery to > 500 cells/μL by Day 28 post HSCT. Secondary graft failure is defined as initial neutrophil engraftment followed by subsequent decline in absolute neutrophil counts < 500 cells/μL, unresponsive to growth factor therapy, but cannot be explained by disease relapse or medications up to two years post-transplant.
Measured: Day 28 and up to 2 years post-transplant (Day 0)
Disease Relapse or Progression
Defined by the protocol.
Measured: Up to 24 months post-transplant (Day 0)
Non-relapse Mortality
Defined as death without evidence of disease progression or recurrence.
Measured: Up to 24 months post-transplant (Day 0)
Toxicity and Infections
All Grade 2-5 toxicities according to CTCAE, version 5.0 will be tabulated for each intervention arm. The proportion of participants developing at least a Grade 2 or higher toxicity across intervention arms will be compared.
Measured: Up to 24 months post-transplant (Day 0)
Disease-Free Survival
Defined as the time from date of transplant to death or relapse/progression, whichever comes first.
Measured: Up to 24 months post-transplant (Day 0)
Overall Survival
Defined as the time interval between date of transplant and death from any cause.
Measured: Up to 24 months post-transplant (Day 0)
Modified Lee Chronic GVHD Symptom Scale (mLSS)
The modified Lee chronic GVHD symptom scale (mLSS) is a 28 item measure with seven domains referent to the past seven days: skin, mouth, eye, lung, psychoemotional, vitality and nutrition.
Measured: Up to 24 months post-transplant (Day 0)
Individual Symptom Scale: Modified Medical Research Council (mMRC) Dyspnea scale
mMRC dyspnea scale assesses the degree of functional disability due to dyspnea.
Measured: Up to 24 months post-transplant (Day 0)
Individual Symptom Scale: Two items from a protocol defined survey
Two items from a protocol defined survey are used to measure hemorrhagic cystitis symptom burden.
Measured: Up to 24 months post-transplant (Day 0)
Individual Symptom Scale: Oral Health Impact Profile (OHIP)
OHIP measures dysfunction, discomfort and disability caused by oral conditions.
Measured: Up to 24 months post-transplant (Day 0)
Individual Symptom Scale: Ocular Surface Disease Index (OSDI)
OSDI measures symptoms and vision effects of dry eye disease.
Measured: Up to 24 months post-transplant (Day 0)
Work Productivity and Impairment Questionnaire (WPAI)
WPAI measures the impact on ability to work and perform regular activities.
Measured: Up to 24 months post-transplant (Day 0)
Comprehensive Score for Financial Toxicity (COST)
COST measures the impacts of treatment on finances and economic status of the patient households.
Measured: Up to 24 months post-transplant (Day 0)
Patient-Reported Economic, Income and Insurance Data (PREIID)
PREIID measures the impacts of treatment on finances and economic status of the patient households.
Measured: Up to 24 months post-transplant (Day 0)
Patient Reported Caregiver Assessment (PRCA)
PRCA measures the type of support provided by caregivers, and the economic burden to patient caregivers.
Measured: Up to 24 months post-transplant (Day 0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2024
- Study start2 Apr 2025
- Primary completion17 Jan 2031 (estimated)
- Study completion17 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft-versus-host Disease (GVHD)Studies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 572 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Blood and Marrow Transplant Clinical Trials Network, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Incyte Medical Monitor, Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06615050
- Sponsor's protocol ID
- INCB18424-370
- Other IDs
- BMT CTN Protocol 2203
- Status last verified
- Oct 2026
- First submitted
- 6 Sep 2024
- Last updated
- 22 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency