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Post-transplant cyclophosphamide strategies to prevent graft-versus-host disease after mismatched unrelated donor stem cell transplant

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

Phase 2 Interventional Center for International Blood and Marrow Transplant Research · NCT06859424

This platform tests whether adding different drug combinations with post-transplant cyclophosphamide prevents graft‑versus‑host disease better than the standard regimen for adults getting mismatched unrelated donor peripheral blood stem cell transplants for blood cancers.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment358 (estimated)
Ages18 Years to 66 Years
SexAll
SponsorCenter for International Blood and Marrow Transplant Research Research network
Drugs / interventionschemotherapy, cyclophosphamide
Locations13 sites (Birmingham, Alabama and 12 other locations)
Trial IDNCT06859424 on ClinicalTrials.gov

What this trial studies

This platform protocol compares post‑transplant cyclophosphamide (PTCy)‑based drug combinations to a standard GVHD prophylaxis regimen in patients receiving mismatched unrelated donor peripheral blood stem cell transplants for hematologic malignancies. Eligible participants receive myeloablative or reduced‑intensity conditioning and are assigned to the control arm or to one of multiple investigational arms (ACCEL‑001, ACCEL‑002, with others possible over time). The protocol collects clinical outcomes, safety data, patient‑reported physical and emotional well‑being, and blood and stool samples, and uses a shared comparator arm to compare new regimens. Investigational arms specify their own dosing, endpoints, and sample size calculations within the platform framework.

Who should consider this trial

Good fit: Adults (per protocol age limits for conditioning type) with AML, ALL, MDS, or CML planning a mismatched unrelated donor (4/8–7/8) T‑cell–replete peripheral blood stem cell transplant after myeloablative or reduced‑intensity conditioning and with HCT‑CI <5 are the intended candidates.

Not a fit: Patients who have fully matched related donors, are receiving non‑PBSC grafts (e.g., cord blood or bone marrow), exceed the trial age or comorbidity criteria, or have nonmalignant indications are unlikely to benefit from these investigational arms.

Why it matters

Potential benefit: If successful, these regimens could reduce the frequency and severity of acute and chronic GVHD and improve survival and quality of life after mismatched unrelated donor transplant.

How similar studies have performed: PTCy has shown promising results reducing GVHD in haploidentical and some unrelated‑donor transplants, but using a platform to test multiple PTCy‑based combinations specifically in mismatched unrelated donor PBSC transplants is a more recent and less extensively proven approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria, MAC RECIPIENTS:

1. Age 18 to \< 66 years (chemotherapy-based conditioning) or \< 61 years (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 (see Table 8 in Section 7.4 for allowed MAC regimens)
5. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age 16-35
6. Product planned for infusion is MMUD T-cell replete PBSC as allograft
7. HCT-CI \< 5 (Appendix H - Hematopoietic Cell Transplant Comorbidity Index Scoring). 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. AML, ALL, or other acute leukemia in first remission or beyond with ≤ 5% marrow blasts and no circulating blasts or evidence of extramedullary 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% vs 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 PFT results
12. Liver function acceptable per local institutional guidelines
13. KPS of ≥ 70% (Appendix I - Performance Status)

Inclusion Criteria, RIC/NMA RECIPIENTS:

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 (see
5. Table 9 in Section 7.4 for allowed NMA/RIC regimens)
6. Available partially HLA-MMUD (4/8-7/8 at HLA-A, -B, -C, and -DRB1 is required) with age 16-35
7. Product planned for infusion is MMUD T-cell replete PBSC allograft
8. 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% vs 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 chronic myelomonocytic leukemia (CMML) according to CMML-specific prognostic scoring system or high-risk MDS/myeloproliferative neoplasms (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.
   6. Patients with primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia, polycythemia vera or MDS with grade 4 fibrosis.
9. Cardiac function: Left ventricular ejection fraction ≥ 40% based on most recent echocardiogram or MUGA results with no clinical evidence of heart failure
10. Estimated creatinine clearance ≥ 45mL/min calculated by equation
11. Pulmonary function: DLCO corrected for hemoglobin ≥ 50% and FEV1 predicted ≥ 50% based on most recent PFT results
12. Liver function acceptable per local institutional guidelines
13. KPS of ≥ 60% (Appendix I - Performance Status)

Exclusion Criteria:

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. Subjects who are breastfeeding or pregnant
6. Uncontrolled bacterial, viral or fungal infection at the time of the transplant preparative regimen
7. Concurrent enrollment on a GVHD prevention clinical trial
8. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant
9. Patients who are HIV-positive 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.

Where this trial is running

Birmingham, Alabama and 12 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.
View on ClinicalTrials.gov → Find more trials like this →
Conditions AMLAcute Lymphoid LeukemiaAcute LeukemiaMDSCMLCLLProlymphocyctic LeukemiaChronic Myelomonocytic Leukemia
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.