TAC/MTX vs. TAC/MMF/PTCY for Prevention of Graft-versus-Host Disease and Microbiome and Immune Reconstitution Study (BMT CTN 1703/1801)

Not Recruiting

Trial ID: NCT03959241


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.

Official 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 (BMT CTN 1703; Progress III); Companion Study: Microbiome and Immune Reconstitution in Cellular Therapies and Hematopoietic Stem Cell Transplantation (BMT CTN 1801; Mi-Immune)

Stanford Investigator(s)

Andrew Rezvani, M.D.
Andrew Rezvani, M.D.

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Ami Bhatt
Ami Bhatt

Associate Professor of Medicine (Hematology) and of Genetics


Inclusion Criteria:

   1. Age 18.0 years or older at the time of enrollment on Segment A

   2. Patients with acute leukemia or chronic myelogenous leukemia with no circulating
   blasts and with less than 5% blasts in the bone marrow

   3. Patients with 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% vs. 5-10% blasts in
   this disease)

   4. Patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma with
   chemosensitive disease at time of transplantation

   5. Patients with 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] with chemosensitive disease at the time
   of transplantation

   6. Planned reduced intensity conditioning regimen (see eligible regimens in Table 2.4a)

   7. Patients must have a related or unrelated peripheral blood stem cell donor as follows:

      1. 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.

      2. 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.

   8. Cardiac function: Left ventricular ejection fraction at least 45%

   9. Estimated creatinine clearance acceptable per institutional guidelines

10. 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%

11. Liver function acceptable per institutional guidelines

12. Karnofsky Performance Score at least 60%

13. Female patients (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)

14. Male patients (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

15. 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. Please
   note that THIS DOES NOT INCLUDE INVESTIGATIONAL AGENTS and maintenance therapy with
   investigational treatment requires approval by the study chairs.

16. 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 patient at any time without prejudice to future
   medical care.

Exclusion Criteria:

   1. Prior allogeneic transplant

   2. Active central nervous system (CNS) involvement by malignant cells

   3. Patients with secondary acute myeloid leukemia arising from myeloproliferative
   disease, including chronic myelomonocytic leukemia (CMML)

   4. Patients with uncontrolled bacterial, viral or fungal infections (currently taking
   medication and with progression or no clinical improvement) at time of enrollment.

   5. Presence of clinically significant fluid collection (ascites, pleural or pericardial
   effusion) that interferes with methotrexate clearance or makes methotrexate use

   6. Patients seropositive for human immunodeficiency virus (HIV) with detectable viral
   load. HIV+ patients with an undetectable viral load on antiviral therapy are eligible.

   7. 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

   8. Female patients who are pregnant (as per institutional practice) or lactating

   9. Patients with a serious medical or psychiatric illness likely to interfere with
   participation in this clinical study

10. Patients 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.

11. Planned use of antithymocyte globulin (ATG) or alemtuzumab in conditioning regimen


procedure: Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate

drug: Tacrolimus

drug: Methotrexate

procedure: Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide

drug: Tacrolimus

drug: Mycophenolate Mofetil

drug: Cyclophosphamide

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Lindsay Danley
(650) 736-0304

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