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

Study Comparing Two Treatments for Blood Cell Transplant

V
Varun Mittal

Primary Investigator

Recruiting
18 years - 100 years
All
Phase 3
10 participants needed
1 Location

Brief description of study

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.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

The primary objective of the Phase III portion of the trial is to compare GVHD-free survival (GFS) up to 24 months after hematopoietic cell transplantation (HCT) between the two GVHD prophylaxis regimens. An event for this time-to-event outcome is defined as Grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, or death by any cause. Secondary objectives are to describe for each treatment arm rates of Grade II-IV and III-IV acute GVHD, rates of NIH mild, moderate, and severe chronic GVHD, hematologic recovery (neutrophil and platelet), lymphocyte recovery, proportion of participants with full or mixed donor chimerism or graft rejection, disease relapse or progression, non-relapse mortality, incidence of biopsy-confirmed post-transplant lymphoproliferative disorders (PTLD), incidence of infections, GVHD-free, relapse-free survival (GRFS), graft failure, toxicity, disease-free survival, overall survival, and patient reported outcomes (PRO).

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Cancer, Graft-versus-host Disease, GVHD, Leukemia, Lymphoma, Allogeneic Peripheral Blood Stem Cell Transplantation
  • Age: 18 years - 100 years
  • Gender: All

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.

Updated on 07 Jul 2025. Study ID: CTO-BMTCTN2203-001, 26681

This study investigates the effectiveness of two different treatment regimens for patients undergoing allogeneic peripheral blood stem cell transplantation. The purpose is to compare the outcomes of using Tacrolimus/Methotrexate/Ruxolitinib versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in patients who receive non-myeloablative or reduced intensity conditioning. This type of transplantation involves using donor stem cells to replace diseased or damaged bone marrow.

Participants will be randomly assigned to one of the two treatment arms. The study will monitor outcomes such as survival without graft-versus-host disease (GVHD), which is a condition where the donor's immune cells attack the recipient's body. Other procedures include assessing recovery of blood cells, incidence of infections, and overall survival. These procedures help to understand the safety and effectiveness of the treatments being studied.

  • Who can participate: Participants must be 18 years or older and undergoing allogeneic stem cell transplantation for certain types of leukemia or lymphoma. They must have a suitable donor and meet specific health criteria, including adequate heart, kidney, and liver function.
  • Study details: Participants will be randomly assigned to receive one of the two investigational treatment regimens. They will receive medications as part of their transplant process and will be monitored for various health outcomes. A placebo is not used in this study.
  • Study timelines: The study will last 24 months.

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