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

NCT ID: NCT06904482

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-13
• Study Completion Date: 2030-02-25

Brief Summary

The purpose of this study is to see if see if adding the specific combination of donors can result in acceptable levels of survival without evidence of disease.

Detailed Description

Cord blood (CB) and haplo-identical grafts are valuable alternative graft sources for patients with hematologic malignancies in need of allogeneic transplantation who lack human leukocyte antigen (HLA)-matched adult donors. In Black, Asian, Hispanic populations, the chance of finding a HLA matched donor is 23%, 41%, and 46%, respectively. These graft sources allow for greater HLA difference between donor and recipient, and increase the availability of donors, and therefore transplant, to these populations. Comparative retrospective analyses demonstrate similar results when compared to haplo/cord transplants. In this variant of the standard haplo/cord transplant, investigators will utilize post-transplant cyclophosphamide aGVHD prophylaxis after infusion of the haplo-identical graft and then infuse the CB graft after completion of post-transplant cyclophosphamide. Our hypothesis is that the combination of these two graft sources in which the haplo-identical graft is unmanipulated and the CB graft is infused after post-transplant cyclophosphamide, will be safe and result in effective disease eradication as measured by progression free survival in high risk patients.

Conditions

aGVHD; Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Haplo-Identical / Cord Blood Transplant

Group Type: EXPERIMENTAL

Haplo-Identical / Cord Blood Transplant

Intervention Type: BIOLOGICAL

Cord Blood Unit Selection Cord Blood Unit Selection should be consistent with published guidelines5 with the understanding that the goal cell dose is 1x105 CD34 cells/kg in this protocol. ABO matching and donor specific antibodies should be taken into account in the selection of the CB unit.

Haplo-Donor Selection Haplo-identical siblings and younger male donors are preferred. ABO matching, CMV compatibility, and donor specific antibodies should be taken into account in the selection of the donor.

Interventions

Haplo-Identical / Cord Blood Transplant

Cord Blood Unit Selection Cord Blood Unit Selection should be consistent with published guidelines5 with the understanding that the goal cell dose is 1x105 CD34 cells/kg in this protocol. ABO matching and donor specific antibodies should be taken into account in the selection of the CB unit.

Haplo-Donor Selection Haplo-identical siblings and younger male donors are preferred. ABO matching, CMV compatibility, and donor specific antibodies should be taken into account in the selection of the donor.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. 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)
• Participant 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 Participant 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.

2. Age > 18 years

3. Participants without a suitable HLA-matched related or unrelated donor

4. Participant with the following suitable grafts:

• A 4-8/8 HLA high resolution matched CB 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/kg)

5. 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.

6. Participants must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. 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

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.

3. Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with RIC have the significant potential for teratogenic or abortifacient effects.

4. 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 subject; or interfere with interpretation of study data.

5. Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

6. Prior autologous stem cell transplant or CAR-T within the preceding 6 months or prior allogeneic transplant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leland Metheny, MD

Role: PRINCIPAL_INVESTIGATOR

Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center

Locations

Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center Seidman Cancer Center

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Leland Metheny, MD

Role: CONTACT

Leland.Metheny@uhhospitals.org

216-844-0139

Facility Contacts

Leland Metheny, MD

Role: primary

Other Identifiers

CASE9Z24

Identifier Type: -

Identifier Source: org_study_id