Calcineurin Inhibitor-Free Interventions BMT CTN 1301 for Prevention of Graft-versus-Host Disease (BMT CTN 1301)
A Randomized, Multi-Center, Phase III Trial of Calcineurin Inhibitor-Free Interventions for Prevention of Graft-versus-Host Disease (BMT CTN 1301; Progress II)
2 other identifiers
interventional
346
1 country
28
Brief Summary
The study is designed as a three arm randomized Phase III, multicenter trial comparing two calcineurin inhibitor (CNI)-free strategies for Graft-versus-Host Disease (GVHD) prophylaxis to standard tacrolimus and methotrexate (Tac/Mtx) in patients with hematologic malignancies undergoing myeloablative conditioning hematopoietic stem cell transplantation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2015
Longer than P75 for phase_3
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 22, 2015
CompletedFirst Posted
Study publicly available on registry
January 26, 2015
CompletedStudy Start
First participant enrolled
August 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 5, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 5, 2020
CompletedResults Posted
Study results publicly available
December 21, 2021
CompletedMarch 7, 2023
March 1, 2023
5.2 years
January 22, 2015
October 6, 2021
March 2, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Chronic GVHD-free, Relapse-free Survival (CRFS) Probability
The primary endpoint of the trial is Chronic GVHD/Relapse-Free Survival (CRFS), treated as a time to event variable. An event for this time to event outcome is defined as moderate to severe chronic GVHD, disease relapse, or death by any cause. Participant will be censored if lost to follow up prior to 2 years. Time is from randomization to the event of moderate to severe chronic GVHD, disease relapse, death, last follow up, or 2 years, whichever comes first. The primary analysis is performed using the intent-to-treat principle (ITT) so that all randomized patients are included in the analysis.
2 years
Secondary Outcomes (20)
Percentage of Participants With Overall Survival (OS)
2 Years
Percentage of Participants With Relapse-free Survival
2 Years
Percentage of Participants With Treatment-related Mortality
2 Years
Participants With Immunosuppression-free Survival
1 Year
Percentage of Participants With Disease Relapse
2 Years
- +15 more secondary outcomes
Study Arms (3)
Tacrolimus/Methotrexate Control Arm
ACTIVE COMPARATORUnmanipulated bone marrow graft with Tacrolimus/Methotrexate GVHD prophylaxis. Tacrolimus will be maintained at therapeutic doses for a minimum of 90 days. Methotrexate will be dosed at 5-15mg/m\^2 for a maximum of 4 doses post-transplant. Cyclosporine may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
CD34 Selection Arm
EXPERIMENTALMobilized CD34-selected Peripheral Blood Stem Cell graft Following screening and enrollment, the donor of patients randomized to the CD34-selection arm will receive mobilization therapy with once daily Granulocyte Colony Stimulating Factor (G-CSF). Mobilization will begin on Day -5 prior to the patient's transplant date. Leukapheresis will be performed on a continuous flow cell separator according to institutional standards and will commence on the morning of the fifth day of G-CSF treatment. The anti-coagulant used for the procedure will be acid citrate dextrose (ACD). Decisions concerning the need for further product collection will be based on the known or projected enriched CD34+ cell content of the previously collected products.
Post Transplant Cyclophosphamide
EXPERIMENTALUnmanipulated Bone Marrow Graft with Cyclophosphamide
Interventions
Unmanipulated BM grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Mobilized CD34-selected PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Unmanipulated BM grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Mesna will be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide or administered per institutional standards. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of Mesna is equal to 80% of the total daily dose of cyclophosphamide. Cyclophosphamide 50 mg/kg will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).
Tacrolimus will be given orally or intravenously per institutional standards starting Day -3. The dose of tacrolimus may be rounded to the nearest 0.5 mg for oral formulations. Subsequent dosing will be based on blood levels, with a target of 5-15 ng/ml. If patients are on medications which alter the metabolism of tacrolimus (e.g. azoles), the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.
Methotrexate will be administered at the doses of 15 mg/m\^2 IV bolus on Day +1, and 10 mg/m\^2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of methotrexate should be given at least 24 hours after the hematopoietic stem cell infusion. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices. Leucovorin rescue is allowed according to institutional practices.
Eligibility Criteria
You may qualify if:
- Males and females aged ≥ 1.0 year and \< 66.0 years
- Patients with acute leukemia in morphologic complete remission with or without hematologic recovery or with myelodysplasia (MDS) with no circulating blasts and with less than 5% blasts in the bone marrow. Patients with CMML must have a WBC count ≤ 10,000 cells/µL and \< 5% blasts in the marrow. Patients with ≥ 5% blasts due to a regenerating marrow must contact the protocol chairs for review.
- Planned myeloablative conditioning regimen
- Patients must have a related or unrelated donor as follows:
- Related donor must be an 8/8 match for human leukocyte antigen (HLA)-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing. Pediatric related donors must weigh ≥ 25.0 kg., must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter, must be willing to (1) donate bone marrow and (2) receive G-CSF followed by donation of peripheral blood stem cells (product to be determined by randomization post enrollment) and must meet institutional criteria for donation.
- Unrelated donor must be an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be medically eligible to donate according to National Marrow Donor Program (NMDP) (or equivalent donor search organization) criteria. At time of enrollment, the donor should not have any known preferences or contraindications to donate bone marrow or peripheral blood stem cells. (Selection of unrelated donors is to be performed according to institutional practice. It is recommended that the time from collection to initiation of the cell processing be considered when prioritizing donors, as data shows better results for CD34 selection when cell processing begins within 36 hours of the end of collection)
- Cardiac function: Ejection fraction at rest ≥ 45.0% or shortening fraction of ≥ 27.0% by echocardiogram or radionuclide scan (MUGA).
- Estimated creatinine clearance (for patients \> 12 years) greater than 50.0 mL/minute (using the Cockcroft-Gault formula and actual body weight); for pediatric patients (\> 1 year to 12 years), Glomerular Filtration Rate (GFR) estimated by the updated Schwartz formula ≥ 90.0 mL/min/1.73 m\^2. If the estimated creatinine clearance is \< 90 mL/min/1.73 m\^2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 70.0 mL/min/1.73 m\^2.
- Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 50% (adjusted for hemoglobin), and forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) ≥ 50%; for children who are unable to perform for Pulmonary Function Tests (PFTs) due to age or developmental ability, there must be no evidence of dyspnea and no need for supplemental oxygen, as evidenced by O2 saturation ≥ 92% on room air.
- Liver function: total bilirubin \< 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \< 2.5x the upper limit of normal.
- Signed informed consent.
You may not qualify if:
- Prior autologous or allogeneic hematopoietic stem cell transplant
- Karnofsky or Lansky Performance Score \< 70%
- Active central nervous system (CNS) involvement by malignant cells
- Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
- Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
- Patients seropositive for HIV-1 or -2
- Patients seropositive for Human T-Lymphotrophic Virus (HTLV)-I or -II
- Patients with active Hepatitis B or C viral replication by polymerase chain reaction (PCR)
- Documented allergy to iron dextran or murine proteins
- Women who are pregnant (positive serum or urine βHCG) or breastfeeding
- Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use 2 effective forms of birth control or abstinence for one year after transplantation
- History of uncontrolled autoimmune disease or on active treatment
- Patients with prior malignancies, except resected non-melanoma 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 will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
- Patient unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests
- Planned post-transplant maintenance therapy except for FLT3 inhibitors or TKIs must be declared prior to randomization.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (28)
City of Hope National Medical Center
Duarte, California, 91010-3000, United States
Stanford Hospital and Clinics
Stanford, California, 94305, United States
University of Florida College of Medicine
Gainesville, Florida, 32610-0277, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612, United States
Blood & Marrow Transplant Program at Northside Hospital
Atlanta, Georgia, 30342, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242, United States
University of Kansas Hospital
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Johns Hopkins/SKCCC
Baltimore, Maryland, 21231, United States
Dana Farber Cancer Institute/Brigham & Women's
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute/Massachusetts General Hospital
Boston, Massachusetts, 02115, United States
Mayo Clinic - Rochester
Rochester, Minnesota, 55905, United States
Washington University/Barnes Jewish Hospital
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198-7680, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021, United States
Columbia University Medical Center
New York, New York, 10032, United States
Weill Cornell Medical Center/New York Presbyterian
New York, New York, 10065, 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, 44106-5061, United States
Ohio State/Arthur G. James Cancer Hospital
Columbus, Ohio, 43210, United States
University of Oklahoma
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and 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
Virginia Commonwealth University/MCV Hospitals
Richmond, Virginia, 23298, United States
University of Wisconsin Hospital & Clinics
Madison, Wisconsin, 53792, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53211, United States
Related Publications (2)
Luznik L, Pasquini MC, Logan B, Soiffer RJ, Wu J, Devine SM, Geller N, Giralt S, Heslop HE, Horowitz MM, Jones RJ, Litzow MR, Mendizabal A, Muffly L, Nemecek ER, O'Donnell L, O'Reilly RJ, Palencia R, Schetelig J, Shune L, Solomon SR, Vasu S, Ho VT, Perales MA. Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. J Clin Oncol. 2022 Feb 1;40(4):356-368. doi: 10.1200/JCO.21.02293. Epub 2021 Dec 2.
PMID: 34855460DERIVEDDel Pozo Martin Y. 47th Annual Meeting of the EBMT. Lancet Haematol. 2021 May;8(5):e317-e318. doi: 10.1016/S2352-3026(21)00104-6. Epub 2021 Mar 31. No abstract available.
PMID: 33811823DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Mendizabal, PhD
- Organization
- The Emmes Company
Study Officials
- STUDY DIRECTOR
Mary Horowitz, MD
Center for International Blood and Marrow Transplant Research
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 22, 2015
First Posted
January 26, 2015
Study Start
August 1, 2015
Primary Completion
October 5, 2020
Study Completion
October 5, 2020
Last Updated
March 7, 2023
Results First Posted
December 21, 2021
Record last verified: 2023-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- Within 6 months of official study closure at participating sites.
- Access Criteria
- Available to the public
Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).