HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation With Reduced Dose Post Transplantation Cyclophosphamide GvHD Prophylaxis
NCT ID: NCT06001385
Last Updated: 2025-05-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2
313 participants
INTERVENTIONAL
2023-12-08
2026-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
* Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days after transplant?
* Does a reduced dose of PTCy maintain the same level of protection against Graft Versus Host Disease (GvHD) as the standard dose of PTCy?
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
High Dose Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil in Preventing Graft Versus Host Disease in Patients With Hematological Malignancies Undergoing Myeloablative or Reduced Intensity Donor Stem Cell Transplant
NCT03128359
A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation
NCT06859424
Graft Versus Host Disease-Reduction Strategies for Donor Blood Stem Cell Transplant Patients With Acute Leukemia or Myelodysplastic Syndrome (MDS)
NCT03970096
Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies
NCT01056614
Busulfan, Cyclophosphamide, & Antithymocyte Globulin Followed by Stem Cell Transplant in Treating Hematologic Cancer
NCT00611351
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Regimen A (MAC: Busulfan and Fludarabine, PBSC HCT; Reduce Dose PTCy
Patients Receive:
Patients receive:
Busulfan (≥ 9 mg/kg total dose) IV or PO on days -6 to -3 Fludarabine (150 mg/m2 total dose) IV on days -6 to -2
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Busulfan
Given IV or PO pre-transplant as part of conditioning regimen
Fludarabine
Given IV pre-transplant as part of conditioning regimen
PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Post-Transplant Cyclophosphamide
Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.
First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.
Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Regimen B (MAC: Fludarabine and TBI, PBSC HCT; Reduce Dose PTCy
Patients receive:
Fludarabine (90 mg/m2 total dose) IV on days -7 to -5 Total body irradiation (TBI) (1200 cGy total dose) on days -4 to -1
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Fludarabine
Given IV pre-transplant as part of conditioning regimen
PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Post-Transplant Cyclophosphamide
Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.
First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.
Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Total-body irradiation
Administered pre-transplant as part of conditioning regimen
Regimen C (RIC: Fludarabine and Busulfan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150-180 mg/m2 total dose) IV on days -6 to -2 Busulfan (less than or equal to 8 mg/kg PO or 6.4 mg/kg IV) on days -5 and -4
Patients receive a peripheral blood stem cell (PBSC) graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Busulfan
Given IV or PO pre-transplant as part of conditioning regimen
Fludarabine
Given IV pre-transplant as part of conditioning regimen
PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Post-Transplant Cyclophosphamide
Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.
First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.
Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Regimen D (RIC: Fludarabine and Melphalan; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (125-150 mg/m2 total dose) IV on days -7 to -3 Melphalan (100-140 mg/m2) IV on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Fludarabine
Given IV pre-transplant as part of conditioning regimen
PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Post-Transplant Cyclophosphamide
Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.
First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.
Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Melphalan
Given IV pre transplant as part of conditioning regimen
Regimen E (NMA: Fludarabine, Cyclophosphamide, and TBI; PBSCT HCT; Reduced Dose PTCy
Patients receive:
Fludarabine (150mg/m2 total dose) IV on days -6 to -2 Cyclophosphamide (29-50mg/kg) IV on days -6 and -5 TBI (200cGy) on day -1
Patients receive a PBSC graft infusion from a mismatched unrelated donor on Day 0.
Patients receive a reduced dose of cyclophosphamide (25mg/kg per dose) on Day 3 and Day 4 post-transplant.
First 20 patients with a 4-6/8 mismatched unrelated donor will receive an alternate dose of post-transplant cyclophosphamide of 37.5 mg/kg on Days 3 and Day 4 post-transplant.
Fludarabine
Given IV pre-transplant as part of conditioning regimen
PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Post-Transplant Cyclophosphamide
Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.
First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.
Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post cyclophosphamide.
Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Total-body irradiation
Administered pre-transplant as part of conditioning regimen
Cyclophosphamide
Given IV pre-transplant as part of conditioning regimen
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Busulfan
Given IV or PO pre-transplant as part of conditioning regimen
Fludarabine
Given IV pre-transplant as part of conditioning regimen
PBSC Hematopoietic Stem Cell Transplantation (HSCT)
Peripheral blood stem cell graft is infused from a mismatched unrelated donor on Day 0
Post-Transplant Cyclophosphamide
Cyclophosphamide (25mg/kg) is administered on Day 3 and Day 4 post-transplant as an IV infusion over 1-2 hours.
First 20 subjects with a 4-6/8 HLA mismatched unrelated donor will receive an intermediate dose of post-transplant cyclophosphamide of 37.5 mg/kg Day 3 and Day 4 post-transplant.
Mesna
Mesna is given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post cyclophosphamide.
Tacrolimus
Tacrolimus is given at a dose of 0.05 mg/kg PO or an IV dose of 0.03 mg/kg of ideal body weight (IBW) starting on Day +5 post-transplant with taper recommended at Day + 90 and finished by Day +180.
Mycophenolate Mofetil
Mycophenolate mofetil (MMF) is given at a dose of 15 mg/kg three times daily IV or PO from Day +5 to Day +35 post-transplant.
Patient Reported Outcomes
Survey assessments will be administered to study participants pre transplant, at Day + 100, Day + 180, and Day +365 post transplant.
Melphalan
Given IV pre transplant as part of conditioning regimen
Total-body irradiation
Administered pre-transplant as part of conditioning regimen
Cyclophosphamide
Given IV pre-transplant as part of conditioning regimen
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and institutional requirements.
3. Stated willingness to comply with all study procedures and availability for the duration of the study.
4. Planned MAC regimen as defined per study protocol
5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
6. Product planned for infusion is MMUD T-cell replete PBSC allograft
7. HCT-CI \< 5. The presence of prior malignancy will not be used to calculate HCT-CI for this trial to allow for the inclusion of patients with secondary or therapy-related AML or MDS.
8. One of the following diagnoses:
1. Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or other acute leukemia in 1st remission or beyond with ≤ 5% marrow blasts and no circulating blasts or evidence of extra-medullary disease. Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
2. Patients with MDS with no circulating blasts and with \< 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \< 5% or 5-10% blasts in MDS). Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
9. Cardiac function: Left ventricular ejection fraction ≥ 45% based on most recent echocardiogram or multi-gated acquisition scan (MUGA) results.
10. Estimated creatinine clearance ≥ 45mL/min calculated by equation.
11. Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin \> 50% and forced expiratory volume in first second (FEV1) predicted \> 50% based on most recent pulmonary function test (PFT) results
12. Liver function acceptable per local institutional guidelines
13. KPS of ≥ 70%
1. Age ≥18 years at the time of signing informed consent
2. Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
3. Stated willingness to comply with all study procedures and availability for the duration of the study.
4. Planned NMA/RIC regimen per study protocol
5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
6. Product planned for infusion is MMUD T-cell replete PBSC allograft
7. One of the following diagnoses:
1. Patients with acute leukemia or chronic myeloid leukemia (CML) with no circulating blasts, no evidence of extramedullary disease, and with \< 5% blasts in the bone marrow.
Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
2. Patients with MDS with no circulating blasts and with \< 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \< 5% or 5-10% blasts in MDS.) Documentation of bone marrow assessment will be accepted within 45 days prior to the anticipated start of conditioning.
3. Patients with chronic lymphocytic leukemia (CLL) or other leukemias (including prolymphocytic leukemia) with chemosensitive disease at time of transplantation
4. Higher risk CMML according to CMML-specific prognostic scoring system or high risk MDS/MPN not otherwise specified are eligible, provided there is no evidence of high-grade bone marrow fibrosis or massive splenomegaly at the time of enrollment.
5. Patients with lymphoma with chemosensitive disease at the time of transplantation
8. Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
9. Estimated creatinine clearance ≥ 45mL/min calculated by equation
10. Pulmonary function: DLCO corrected for hemoglobin \> 50% and FEV1 predicted \>50% based on most recent PFT results
11. Liver function acceptable per local institutional guidelines
12. KPS of ≥ 60%
1. Age ≥18 years at the time of signing informed consent
2. Patient or legally authorized representative has the ability to provide informed consent according to the applicable regulatory and local institutional requirements.
3. Stated willingness to comply with all study procedures and availability for the duration of the study.
4. Planned NMA/RIC regimen per study protocol
5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age ≥ 18 and ≤ 40 years (≤ 35 preferred).
6. Product planned for infusion is MMUD T-cell replete PBSC allograft
7. Diagnosis of primary myelofibrosis with risk features making them eligible for HCT. Myelofibrosis secondary to essential thrombocythemia, polycythemia vera, or MDS with grade 4 fibrosis are also eligible. Patients with a myelofibrosis diagnosis require sponsor approval before enrolling.
8. Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
9. Estimated creatinine clearance ≥ 45 mL/min calculated by equation
10. Pulmonary function: DLCO corrected for hemoglobin \> 50% and FEV1 predicted \>50% based on most recent PFT results
11. Liver function acceptable per local institutional guidelines
12. KPS of ≥ 60%
1. Must be unrelated to the subject and high-resolution HLA-matched at 4/8, 5/8, 6/8, or 7/8 (HLA-A, -B, -C, and -DRB1.
2. Donor must be typed at high-resolution for a minimum of HLA-A, -B, -C, -DQB1, and -DPB1.
3. Age ≥ 18 years and ≤ 40 years at the time of signing informed consent for PBSC donation. Note: donors are preferred to be ≤ 35.
4. Meet the donor registries' medical suitability requirements for PBSC donation.
5. Must undergo eligibility screening according to current Food and Drug Administration (FDA) requirements. Donors who do not meet one or more of the donor screening requirements may donate under urgent medical need.
6. Must agree to donate PBSC.
7. Must have the ability to give informed consent according to standard (non-study) informed consent according to applicable donor regulatory requirements.
Exclusion Criteria
2. Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
3. Subjects with a prior allogeneic transplant
4. Subjects with an autologous transplant within the past 3 months
5. Females who are breast-feeding or pregnant
6. Uncontrolled bacterial, viral, or fungal infection at the time of the transplant preparative regimen
7. Concurrent enrollment on a preventative GvHD and/or infectious disease prevention clinical trial.
8. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant.
9. Patients who are HIV+ with persistently positive viral load. HIV-infected patients on effective anti-retroviral therapy (ART) with undetectable viral load within 6 months are eligible for this trial. Patients with well controlled HIV are eligible provided resistance panels are negative, the patient is compliant with ART, and their disease remains well controlled.
1. Donor unwilling or unable to donate.
2. Recipient positive for HLA antibodies against a mismatched HLA in the selected donor determined by the presence of donor specific HLA antibodies (DSA) to any mismatched HLA allele/antigen at any of the following loci (HLA-A, -B, -C, -DRB1, DRB3, DRB4, DRB5, -DQA1, - DQB1, -DPA1, -DPB1) with median fluorescence intensity (MFI) \>3000 by microarray-based single antigen bead testing. In patients receiving red blood cell or platelet transfusions, DSA evaluation must be performed or repeated post-transfusion and prior to donor mobilization and initiation of recipient preparative regimen.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Marrow Donor Program
OTHER
Center for International Blood and Marrow Transplant Research
NETWORK
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Steven Devine, MD
Role: PRINCIPAL_INVESTIGATOR
NMDP
Jeffery Auletta, MD
Role: STUDY_CHAIR
NMDP
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Mayo Clinic Arizona
Phoenix, Arizona, United States
Honor Health
Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
City of Hope
Duarte, California, United States
University of California San Francisco
San Francisco, California, United States
Stanford University
Stanford, California, United States
Colorado Blood Cancer Institute at Presbyterian St. Luke's
Denver, Colorado, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, United States
University of Miami Sylvester Cancer Center
Miami, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University
Atlanta, Georgia, United States
Greenbaum Cancer Center University of Maryland
Baltimore, Maryland, United States
Tufts University
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Barnes Jewish Hospital / Washington University
St Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center - Adults
New York, New York, United States
University of North Carolina
Chapel Hill, North Carolina, United States
Ohio State Medical Center
Columbus, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
The Center for Bone Marrow Transplantation at Geisinger
Danville, Pennsylvania, United States
Abramson Cancer Center
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
TriStar Centennial
Nashville, Tennessee, United States
St. David's South Austin Medical Center
Austin, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
Methodist Hospital San Antonio
San Antonio, Texas, United States
University of Virginia Health System
Charlottesville, Virginia, United States
Fred Hutchinson Cancer Center
Seattle, Washington, United States
Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Karen Ballen, M.D.
Role: primary
Sameem Abedin, MD
Role: primary
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
OPTIMIZE
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.