Myelodysplastic Syndrome Clinical Trial

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

Summary

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.

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Full Description

1703: Graft-versus-Host Disease (GVHD) is a complication that affects many hematopoietic stem cell transplant (HSCT) patients; it occurs when the new cells from a transplant attack the recipient's body. The current standard GVHD prophylaxis regimen for patients with hematologic malignancies undergoing HSCT involves a combination of immunosuppressive agents given for the first 6 months after transplant.

The standard strategy of Tacrolimus/Methotrexate will be used as a control arm in comparison to one other treatment plan utilizing Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide. Study participants will receive an infusion of mobilized peripheral blood stem cell grafts on both arms. Study participants will be randomized to one of these two treatment arms.

1801: A relationship between the intestinal microbiota and graft-versus-host disease (GVHD) has long been appreciated but is still not well understood. Mice transplanted in germ-free conditions or treated with gut-decontaminating antibiotics developed less severe GVHD. Clinical studies initially suggested a benefit from near-total bacterial decontamination, but later showed no clear benefit and this approach was discontinued in the early 1990s. Partial gut decontamination continues to be practiced at many centers. More recently, the advent of next-generation sequencing (NGS) has resulted in cheaper and easier characterization of complex microbial mixtures. This has led to a renewed interest in evaluating the relationship between the microbiota and human health and disease, including recipients of hematopoietic cell transplantation (HCT). Similarly, NGS has also contributed to significant advancements in the investigator's understanding of immune reconstitution in HCT patients and how this may impact clinica outcomes.

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.

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Eligibility Criteria

Inclusion Criteria:

Age 18.0 years or older at the time of enrollment on Segment A
Patients with acute leukemia or chronic myelogenous leukemia with no circulating blasts and with less than 5% blasts in the bone marrow
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)
Patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma with chemosensitive disease at time of transplantation
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
Planned reduced intensity conditioning regimen (see eligible regimens in Table 2.4a)

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

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

Prior allogeneic transplant
Active central nervous system (CNS) involvement by malignant cells
Patients with secondary acute myeloid leukemia arising from myeloproliferative disease, including chronic myelomonocytic leukemia (CMML)
Patients 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
Patients seropositive for human immunodeficiency virus (HIV) with detectable viral load. HIV+ patients 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 patients who are pregnant (as per institutional practice) or lactating
Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study
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.
Planned use of antithymocyte globulin (ATG) or alemtuzumab in conditioning regimen

Study is for people with:

Myelodysplastic Syndrome

Phase:

Phase 3

Estimated Enrollment:

428

Study ID:

NCT03959241

Recruitment Status:

Active, not recruiting

Sponsor:

Medical College of Wisconsin

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There are 37 Locations for this study

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University of Alabama at Birmingham
Birmingham Alabama, 35294, United States
City of Hope National Medical Center
Duarte California, 91010, United States
University of California, San Francisco
San Francisco California, 94143, United States
Stanford Hospital and Clinics
Stanford California, 94305, United States
University of Florida College of Medicine (Shands)
Gainesville Florida, 32610, United States
University of Miami
Miami Florida, 33136, United States
H. Lee Moffitt Cancer Center
Tampa Florida, 33624, United States
Emory University
Atlanta Georgia, 30322, United States
Blood & Marrow Transplant Program at Northside Hospital
Atlanta Georgia, 30342, United States
University of Chicago
Chicago Illinois, 60637, United States
Loyola University
Maywood Illinois, 60153, United States
Indiana University Simon Cancer Center
Indianapolis Indiana, 46202, United States
Indiana BMT - St. Francis Hospital
Indianapolis Indiana, 46327, United States
University of Iowa Hospitals and Clinics
Iowa City Iowa, 52242, United States
University of Kansas Hospital
Kansas City Kansas, 66160, United States
Johns Hopkins University
Baltimore Maryland, 21231, United States
Dana Farber Cancer Institute/Brigham & Women's
Boston Massachusetts, 02115, United States
Dana Farber Cancer Institute/Massachusetts General Hospital
Boston Massachusetts, 02115, United States
University of Michigan
Ann Arbor Michigan, 48109, United States
Karmanos Cancer Institute, Children's Hospital of Michigan
Detroit Michigan, 48201, United States
University of Minnesota
Minneapolis Minnesota, 55455, United States
Mayo Clinic - Rochester
Rochester Minnesota, 55905, United States
Washington University/Barnes Jewish Hospital
Saint Louis Missouri, 63110, United States
Mount Sinai Medical Center
New York New York, 10029, United States
Memorial Sloan-Kettering Cancer Center
New York New York, 10174, United States
University of North Carolina
Chapel Hill North Carolina, 27599, United States
Duke University Medical Center
Durham North Carolina, 27705, United States
University Hospitals of Cleveland/Case Western
Cleveland Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland Ohio, 44195, United States
Ohio State/Arthur G. James Cancer Hospital
Columbus Ohio, 43210, United States
Oregon Health & Science University
Portland Oregon, 97239, United States
University of Pennsylvania Cancer Center
Philadelphia Pennsylvania, 19104, United States
Medical University of South Carolina
Charleston South Carolina, 29425, United States
Baylor College of Medicine/The Methodist Hospital
Houston Texas, 77030, United States
University of Texas, MD Anderson Cancer Research Center
Houston Texas, 77030, United States
Virginia Commonwealth University, MCV Hospital
Richmond Virginia, 23298, United States
Fred Hutchinson Cancer Research Center
Seattle Washington, 98109, United States
University of Wisconsin Hospital & Clinics
Madison Wisconsin, 53792, United States
Medical College of Wisconsin
Milwaukee Wisconsin, 53211, United States

How clear is this clinincal trial information?

Study is for people with:

Myelodysplastic Syndrome

Phase:

Phase 3

Estimated Enrollment:

428

Study ID:

NCT03959241

Recruitment Status:

Active, not recruiting

Sponsor:


Medical College of Wisconsin

How clear is this clinincal trial information?

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