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)

Purpose

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

Condition

  • Graft-versus-host Disease (GVHD)

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 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%. - 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 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. - 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

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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)

Recruiting Locations

Stanford Cancer Center
Palo Alto 5380748, California 5332921 94304

University of California San Francisco
San Francisco 5391959, California 5332921 94158

University of Miami
Miami 4164138, Florida 4155751 33136

Moffitt Cancer Center
Tampa 4174757, Florida 4155751 33612

Blood and Marrow Transplant Group of Georgia
Atlanta 4180439, Georgia 4197000 30342

Indiana University Cancer Center
Indianapolis 4259418, Indiana 4921868 46202

University of Kansas Hospital Authority
Kansas City 4273837, Kansas 4273857 66160

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114

University of Michigan
Ann Arbor 4984247, Michigan 5001836 48109

Karmanos Cancer Institute
Detroit 4990729, Michigan 5001836 48201

Henry Ford Hospital
Detroit 4990729, Michigan 5001836 48202

Washington University
St Louis 4407066, Missouri 4398678 63110

Mount Sinai Hospital
New York 5128581, New York 5128638 10029

Memorial Sloan Kettering
New York 5128581, New York 5128638 10065

University of North Carolina At Chapel Hill
Chapel Hill 4460162, North Carolina 4482348 27514

Levine Cancer Institute
Charlotte 4460243, North Carolina 4482348 28204

Duke University Medical Center
Durham 4464368, North Carolina 4482348 27705

Cleveland Clinic
Cleveland 5150529, Ohio 5165418 44195

Ohio State University
Columbus 4509177, Ohio 5165418 43210

Oregon Health & Science University
Portland 5746545, Oregon 5744337 97239

University of Pennsylvania
Philadelphia 4560349, Pennsylvania 6254927 19104

Medical University of South Carolina
Charleston 4574324, South Carolina 4597040 29425

Vanderbilt Medical Center
Nashville 4644585, Tennessee 4662168 37232

Baylor College of Medicine
Houston 4699066, Texas 4736286 77030

Virginia Commonwealth University, North Hospital
Richmond 4781708, Virginia 6254928 23298

Fred Hutchinson Cancer Research Center
Seattle 5809844, Washington 5815135 98109

University of Wisconsin
Madison 5261457, Wisconsin 5279468 53705

Medical College of Wisconsin
Milwaukee 5263045, Wisconsin 5279468 53226

More Details

NCT ID
NCT06615050
Status
Recruiting
Sponsor
Incyte Corporation

Study Contact

Incyte Corporation Call Center (US)
1.855.463.3463
medinfo@incyte.com

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ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, led by the NIH’s National Center for Advancing Translational Sciences (NCATS), grants UL1TR000445 and 1U54RR032646-01, and grant U24TR001579 from NCATS and the National Library of Medicine. The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH, NCATS, or NLM.

Vanderbilt University Medical Center