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Clinical Trial 20041

Cancer Type: Malignant Hematology
Study Type: Prevention
NCT#: NCT03959241

Phase: Phase III
Prinicipal Investigator:

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Study Title

A Randomized, Multicenter, Phase III Trial of Tacrolimus/Methotrexate versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation


This encompasses two studies: 1703: The study is designed as a randomized, phase III, multicenter trial comparing two acute graft-versus-host disease (aGVHD) prophylaxis regimens: tacrolimus/methotrexate (Tac/MTX) versus post-transplant cyclophosphamide/ tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) in the setting of reduced intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation. 1801: The goal of this protocol is to test the primary hypothesis that the engraftment stool microbiome diversity predicts one-year non-relapse mortality in patients undergoing reduced intensity allogeneic HCT.


The primary objective of the trial is to compare 1 year GVHD-free, relapse-free survival (GRFS) between the two GVHD prophylaxis regimens. An event for this time-to-event outcome is defined as grade III-IV aGVHD, chronic GVHD requiring systemic immune suppression, disease relapse or progression, or death by any cause. Secondary objectives are to describe for each treatment arm rates of grade II-IV and III-IV aGVHD, rates of Minnesota high risk aGVHD, chronic GVHD, immunosuppression-free survival at 1 year, hematologic recovery (neutrophil and platelet), donor cell engraftment, disease relapse or progression, transplant-related mortality, rates of grade 3+ toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, incidence of grade 2-3 infections, immune reconstitution, and overall survival.




Cellcept (Mycophenolate Mofetil); FK506 (Tacrolimus); Mycophenolate Mofetil (); Tacrolimus (); cyclophosphamide (); cytoxan (cyclophosphamide); methotrexate ()

Inclusion Criteria

  • Age 18 years or older at the time of enrollment on Segment A
  • Participants with acute leukemia or chronic myelogenous leukemia with no circulating blasts and with less than 5% blasts in the bone marrow
  • Participants with myelodysplasia 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 > Participants with relapsed chronic lymphocytic leukemia with chemosensitive disease at time of transplantation
  • Participants with lymphoma with chemosensitive disease at the time of transplantation
  • Planned reduced intensity conditioning regimen (see eligible regimens in Table 2.4a)
  • Participants must have a related or unrelated peripheral blood stem cell donor as follows: (a) Sibling donor must be a 6/6 match for Human Leukocyte Antigen-A (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. (b) 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 National Marrow Donor Program (NMDP) criteria for donation.
  • Cardiac function: Left ventricular ejection fraction at least 45%
  • Estimated creatinine clearance acceptable per institutional guidelines
  • Pulmonary function: Diffusing capacity of lung for carbon monoxide (DLCO) corrected for hemoglobin at least 40% and forced expiratory volume at one second (FEV1) predicted at least 50%
  • Liver function acceptable per institutional guidelines
  • Karnofsky Performance Score at least 60%
  • Female participants (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two (2) 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 12 months post-transplant (see Section 2.6.4 for definition of postmenopausal)
  • Male participants (even if surgically sterilized), of partners of women of childbearing potential must agree to one of the following: practice effective barrier contraception (see Section 2.6.4 for list of barrier methods), or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant
  • Plans for the use of post-transplant maintenance therapy must be disclosed upon enrollment and must be used irrespective of the outcome of the randomization
  • 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

    Exclusion Criteria:

  • Prior allogeneic transplant
  • Active central nervous system (CNS) involvement by malignant cells
  • Participants with secondary acute myeloid leukemia arising from myeloproliferative disease, including chronic myelomonocytic leukemia (CMML)
  • Participants with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
  • 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.
  • Myocardial infarction within 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.
  • 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 > Planned use of antithymocyte globulin (ATG) or alemtuzumab in conditioning regimen

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