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 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

Study Overview

• Status: Recruiting
• Conditions: Graft-versus-host Disease (GVHD)
• Intervention / Treatment: Drug: Tacrolimus (Tac); Drug: Methotrexate (MTX); Drug: Ruxolitinib (Rux); Drug: Cyclophosphamide; Drug: Mycophenolate mofetil (MMF)

• Study Type: Interventional
• Enrollment (Estimated): 572
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Incyte Corporation Call Center (US); Phone Number: 1.855.463.3463; Email: medinfo@incyte.com
• Study Contact Backup: Name: Incyte Corporation Call Center (ex-US); Phone Number: +800 00027423; Email: eumedinfo@incyte.com

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Center
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Recruiting
      • Blood and Marrow Transplant Group of Georgia
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Hospital Authority
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Hospital
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina At Chapel Hill
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt Medical Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University, North Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Finding Run-In Group 1: Tac/MTX/Ruxolitnib Dose 1; Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses.	Drug: Tacrolimus (Tac); Tablet or intravenously (IV); Drug: Methotrexate (MTX); Intravenously (IV); Drug: Ruxolitinib (Rux); Tablet; Other Names: Jakafi, INCB018424
Experimental: Dose Finding Run-In Group 2: Tac/MTX/Ruxolitnib Dose 2; Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses.	Drug: Tacrolimus (Tac); Tablet or intravenously (IV); Drug: Methotrexate (MTX); Intravenously (IV); Drug: Ruxolitinib (Rux); Tablet; Other Names: Jakafi, INCB018424
Experimental: Main Study Group A: Tac/MTX/Ruxolitnib; Tacrolimus/ methotrexate/ ruxolitinib (Tac/MTX/Rux) at the protocol defined doses.	Drug: Tacrolimus (Tac); Tablet or intravenously (IV); Drug: Methotrexate (MTX); Intravenously (IV); Drug: Ruxolitinib (Rux); Tablet; Other Names: Jakafi, INCB018424
Active Comparator: Main Study Group B: PTCy/Tac/MMF; Post-transplant cyclophosphamide/ tacrolimus/ mycophenolate mofetil (PTCy/Tac/MMF) at the protocol defined doses.	Drug: Tacrolimus (Tac); Tablet or intravenously (IV); Drug: Cyclophosphamide; Intravenously (IV); Drug: Mycophenolate mofetil (MMF); Tablet or intravenously (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 24 months post-transplant (Day 0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 24 months post-transplant (Day 0)
Incidence of chronic GVHD	Defined by the protocol.	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.	Up to 24 months post-transplant (Day 0)
Time to neutrophil and platelet recovery	Defined by the Protocol.	Up to 24 months post-transplant (Day 0)
Donor Cell Engraftment	Defined by the protocol.	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.	Day 28 and up to 2 years post-transplant (Day 0)
Disease Relapse or Progression	Defined by the protocol.	Up to 24 months post-transplant (Day 0)
Non-relapse Mortality	Defined as death without evidence of disease progression or recurrence.	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.	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.	Up to 24 months post-transplant (Day 0)
Overall Survival	Defined as the time interval between date of transplant and death from any cause.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Up to 24 months post-transplant (Day 0)

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Collaborators: National Cancer Institute (NCI); National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH); Blood and Marrow Transplant Clinical Trials Network
• Investigators: Study Director: Incyte Medical Monitor, Incyte Corporation

Publications and helpful links

Helpful Links

• 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)

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2025
• Primary Completion (Estimated): January 17, 2031
• Study Completion (Estimated): January 17, 2031

Study Registration Dates

• First Submitted: September 6, 2024
• First Submitted That Met QC Criteria: September 25, 2024
• First Posted (Actual): September 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ruxolitinib; Janus kinase inhibitor; steroid-refractory; Chronic GvHD (cGvHD); Graft-versus-host Disease (GVHD)
• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fatty Acids; Lipids; Hydrocarbons; Acids, Acyclic; Carboxylic Acids; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Macrolides; Lactones; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pterins; Pteridines; Aminopterin; Caproates; Methotrexate; Cyclophosphamide; Mycophenolic Acid; Tacrolimus; Triamcinolone; ruxolitinib
• Other Study ID Numbers: INCB18424-370; BMT CTN Protocol 2203 (Other Identifier: Blood and Marrow Transplant Clinical Trials Network)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes