Combining an unmodified family (haplo‑identical) donor graft with cord blood for transplant

Co-Transplant of an Unmodified Haplo-Identical Graft With Cord Blood

This trial will test whether giving an unmodified haplo‑identical donor graft followed by a cord blood graft with post‑transplant cyclophosphamide helps people with high‑risk AML, ALL, or MDS stay free of disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Case Comprehensive Cancer Center (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, radiation, cyclophosphamide
• Locations: 1 site (Cleveland, Ohio)
• Trial ID: NCT06904482 on ClinicalTrials.gov

What this trial studies

Patients who lack HLA‑matched adult donors will receive an unmodified haplo‑identical graft with post‑transplant cyclophosphamide for acute GVHD prevention, and then a cord blood graft will be infused after the cyclophosphamide course. The trial enrolls adults with high‑risk acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), or intermediate‑to‑very high‑risk myelodysplastic syndromes (MDS) who are eligible for allogeneic transplant. Key outcomes include progression‑free survival, engraftment kinetics, rates of acute and chronic GVHD, and transplant‑related mortality. This is a phase 2, single‑center protocol at Case Comprehensive Cancer Center testing safety and efficacy of the co‑transplant sequence.

Who should consider this trial

Good fit: Adults with high‑risk AML or ALL in CR1–CR3/CRi or intermediate‑to‑very high‑risk MDS who lack an HLA‑matched adult donor and are eligible for allogeneic transplantation.

Not a fit: Patients who have a readily available well‑matched HLA adult donor, who are medically ineligible for allogeneic transplant, or who have uncontrolled active infections or disease states outside the listed remission criteria are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could expand curative transplant options for patients without matched donors and improve progression‑free survival.

How similar studies have performed: Retrospective analyses of haplo/cord transplant approaches have shown comparable results to other alternative donor transplants, but this exact sequence with delayed cord infusion after post‑transplant cyclophosphamide is relatively novel with limited prospective data.

Eligibility criteria

Inclusion Criteria:

* Participants with the following hematologic malignancies:

  * Acute myelogenous leukemia (AML): High-risk AML including:

    * Antecedent hematological disease (e.g., myelodysplasia (MDS))
    * Treatment-related
    * Complete Remission (CR1) with poor or intermediate-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23, del 5, del 7, TP53 mutations, complex cytogenetics)
    * Participants must be in CR1, CR2, CR3 or CRi
  * Acute lymphoblastic leukemia (ALL)

    * High-risk CR1 including:

      * Poor-risk cytogenetics (e.g., t(9;22)or 11q23 rearrangements)
      * Presence of minimal disease by flow cytometry or PCR or Clonoseq after 2 or more cycles of chemotherapy
      * No CR within 4 weeks of initial treatment
    * Participants in CR2 or beyond
    * Participants must be in CR1, CR2, CR3, or CRi
  * Myelodysplastic syndromes (MDS), Intermediate, High or Very High Risk by the revised international prognostic scoring system (IPSS-R) or treatment related MDS
  * High-risk lymphoma
* Age \> 18 years
* Participants without a suitable HLA-matched related or unrelated donor CASE9Z24 Page 17 Version dated 12.16.2025
* Participants with the following suitable grafts:

  * A 4-8/8 HLA high resolution matched cord blood unit with a cell dose of 1.0x105 CD34 cells/kg.
  * A haplo-identical donor with a goal cell dose of \> 4.0x106 CD34cells/kg (minimum 2 x106 CD34 cells/kg)
* Concurrent Therapy for Extramedullary Leukemia or CNS Lymphoma: Concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated. Such treatment may continue until the planned course is completed. Participants must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement. Maintenance therapy after transplant is allowed.
* Participants must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Participants with inadequate Organ Function as defined by:

  * Creatinine clearance \< 40ml/min (Cockcroft-Gault)
  * Bilirubin \> 2X institutional upper limit of normal unless Gilbert syndrome
  * AST (SGOT) \> 3X institutional upper limit of normal
  * ALT (SGPT) \> 3X institutional upper limit of normal
  * Pulmonary function: DLCOc \< 60%
  * Cardiac: left ventricular ejection fraction \< 40%
  * ECOG \<2
* Participants with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with RIC have the significant potential for teratogenic or abortifacient effects.
* Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
* Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
* Prior autologous stem cell transplant or CAR-T within the preceding 6 months or prior allogeneic transplant.

Where this trial is running

Cleveland, Ohio

• Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center Seidman Cancer Center — Cleveland, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Leland Metheny, MD — Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center
• Study coordinator: Leland Metheny, MD

Conditions aGVHD; Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndromes; Unmodified Haplo-Identical Graft with Cord Blood; post-transplant cyclophosphamide aGVHD prophylaxis