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Transplantation using HLA-Mismatched Donors with Reduced Cyclophosphamide

A Phase II Study of Reduced Dose Post Transplantation Cyclophosphamide as GvHD Prophylaxis in Adult Patients With Hematologic Malignancies Receiving HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Phase 2 Interventional Center for International Blood and Marrow Transplant Research · NCT06001385

This study is testing if a lower dose of a medication after a stem cell transplant can help patients with blood cancers who receive mismatched donor cells avoid infections while still protecting them from complications.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment313 (estimated)
Ages18 Years and up
SexAll
SponsorCenter for International Blood and Marrow Transplant Research Research network
Drugs / interventionschemotherapy, Cyclophosphamide
Locations32 sites (Phoenix, Arizona and 31 other locations)
Trial IDNCT06001385 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of a reduced dose of Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies who receive stem cell transplants from HLA-mismatched unrelated donors. The study aims to determine if this reduced dosage can lower the risk of infections during the first 100 days post-transplant while still providing adequate protection against Graft Versus Host Disease (GvHD). Participants will undergo a regimen that includes Busulfan, Fludarabine, and PBSC Hematopoietic Stem Cell Transplantation. The trial will assess the outcomes of these interventions in a defined patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 66 with specific hematologic malignancies who can receive stem cells from HLA-mismatched unrelated donors.

Not a fit: Patients outside the specified age range or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to safer transplant procedures with fewer complications for patients with hematologic malignancies.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific methodology is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Stratum 1 Recipient Inclusion Criteria:

1. Age ≥ 18 years and \< 66 years (chemotherapy-based conditioning) or \< 61 years (total body irradiation \[TBI\]-based conditioning) 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 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%

Stratum 2 Recipient Inclusion Criteria:

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%

Stratum 3 Recipient Inclusion Criteria:

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%

Donor Inclusion Criteria (note: donors are not research subjects):

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.

Recipient Exclusion Criteria (Strata 1, 2, and 3):

1. Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
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.

Donor Exclusion Criteria:

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.

Where this trial is running

Phoenix, Arizona and 31 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
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Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.