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Comparing two treatment regimens for Graft-versus-host Disease after stem cell transplantation

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

PHASE3 · Incyte Corporation · NCT06615050

This study is testing two different treatment plans for adults with Graft-versus-host Disease after stem cell transplantation to see which one works better, especially for those who haven't responded to steroids.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment572 (estimated)
Ages18 Years and up
SexAll
SponsorIncyte Corporation (industry)
Drugs / interventionsalemtuzumab, ruxolitinib, methotrexate, Cyclophosphamide
Locations30 sites (Palo Alto, California and 29 other locations)
Trial IDNCT06615050 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of a combination treatment involving Tacrolimus, Methotrexate, and Ruxolitinib against a regimen of Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil in patients undergoing non-myeloablative or reduced intensity conditioning allogeneic peripheral blood stem cell transplantation. The goal is to determine which treatment is more effective in managing Graft-versus-host Disease (GVHD), particularly in patients who are steroid-refractory. Participants must be 18 years or older and have specific hematological conditions requiring stem cell transplantation.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older undergoing allogeneic hematopoietic cell transplantation for specific hematological malignancies.

Not a fit: Patients who do not have a related or unrelated peripheral blood stem cell donor or those with conditions not specified in the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients suffering from Graft-versus-host Disease.

How similar studies have performed: Other studies have shown promise with similar treatment approaches, but this specific combination is being evaluated for the first time in this context.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Palo Alto, California and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Graft-versus-host Disease, Chronic GvHD, steroid-refractory, ruxolitinib, Janus kinase inhibitor

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.