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)

NCT06615050 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: INCB18424-370BMT CTN Protocol 2203
• Study Type: interventional
• Target: 572
• Locations: 1 country
• Sites: 30

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)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• GVHD/relapse or Progression-free Survival (GRFS)

  Up to 24 months post-transplant (Day 0)

• Incidence of chronic GVHD

  Up to 24 months post-transplant (Day 0)

• Incidence of acute grade 2-4 and 3-4 graft versus host disease (GVHD)

  Up to 24 months post-transplant (Day 0)

• Time to neutrophil and platelet recovery

  Up to 24 months post-transplant (Day 0)

• Donor Cell Engraftment

  Up to 24 months post-transplant (Day 0)

Study Arms (4)

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

EXPERIMENTAL

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

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.

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.

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.

Drug: Tacrolimus (Tac); Drug: Cyclophosphamide; Drug: Mycophenolate mofetil (MMF)

Interventions

Ruxolitinib (Rux) DRUG

Tablet

Also known as: Jakafi, INCB018424

Dose Finding Run-In Group 1: Tac/MTX/Ruxolitnib Dose 1; Dose Finding Run-In Group 2: Tac/MTX/Ruxolitnib Dose 2; Main Study Group A: Tac/MTX/Ruxolitnib

Tacrolimus (Tac) DRUG

Tablet or intravenously (IV)

Dose Finding Run-In Group 1: Tac/MTX/Ruxolitnib Dose 1; Dose Finding Run-In Group 2: Tac/MTX/Ruxolitnib Dose 2; Main Study Group A: Tac/MTX/Ruxolitnib; Main Study Group B: PTCy/Tac/MMF

Methotrexate (MTX) DRUG

Intravenously (IV)

Dose Finding Run-In Group 1: Tac/MTX/Ruxolitnib Dose 1; Dose Finding Run-In Group 2: Tac/MTX/Ruxolitnib Dose 2; Main Study Group A: Tac/MTX/Ruxolitnib

Cyclophosphamide DRUG

Intravenously (IV)

Main Study Group B: PTCy/Tac/MMF

Mycophenolate mofetil (MMF) DRUG

Tablet or intravenously (IV)

Main Study Group B: PTCy/Tac/MMF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 creatinine clearance greater than 60 ml/min using the 2021 CKD-EPI formula or 24-hour urine creatinine clearance.
• 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%.

You may not qualify if:

• Prior allogeneic transplant.
• Active CNS involvement by malignant cells.
• Participants with secondary AML arising from myeloproliferative neoplasms or overlap syndromes, including CMML and MDS/MPN syndromes; participants with secondary AML arising from myelodysplastic neoplasm are eligible.
• Participants with primary 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.
• 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator
• Incyte Corporation: lead
• Blood and Marrow Transplant Clinical Trials Network: collaborator

Study Sites (30)

Stanford Cancer Center

Palo Alto, California, 94304, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94158, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

RECRUITING

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kansas Hospital Authority

Kansas City, Kansas, 66160, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

Memorial Sloan Kettering

New York, New York, 10065, United States

RECRUITING

University of North Carolina At Chapel Hill

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27705, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Sarah Cannon

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Virginia Commonwealth University, North Hospital

Richmond, Virginia, 23298, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

RECRUITING

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related 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)

MeSH Terms

Conditions

Graft vs Host Disease; Bronchiolitis Obliterans Syndrome

Interventions

Tacrolimus; Triamcinolone; Methotrexate; ruxolitinib; Cyclophosphamide; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Incyte Medical Monitor

  Incyte Corporation

  STUDY DIRECTOR

Central Study Contacts

Incyte Corporation Call Center (US)

CONTACT

1.855.463.3463; medinfo@incyte.com

Incyte Corporation Call Center (ex-US)

CONTACT

+800 00027423; eumedinfo@incyte.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2024
• First Posted: September 26, 2024
• Study Start: April 2, 2025
• Primary Completion (Estimated): January 17, 2031
• Study Completion (Estimated): January 17, 2031
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• 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.

Locations

US (30)