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

Phase 2

Not yet recruiting

• Conditions: aGVHD; Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndromes
• Interventions: Biological: Haplo-Identical / Cord Blood Transplant

• Registration Number: NCT06904482
• Lead Sponsor: Case Comprehensive Cancer Center

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.

Study Timeline

• Study First Submitted: 2025-03-31
• Study First Submitted QC: 2025-03-31
• Study First Posted: 2025-04-01
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-04
• Last Update Posted: 2025-06-05
• Study Start: 2025-07
• Primary Completion: 2027-02-24
• Study Completion: 2030-02-25

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Haplo-Identical / Cord Blood Transplant	Haplo-Identical / Cord Blood Transplant	-

Primary Outcome Measures

Name	Time	Method
Progression free survival(PFS) at 6 months after transplant	6 months after transplant	Kaplan-Meier method will be used to estimate the PFS

Secondary Outcome Measures

Name	Time	Method
Progression free survival at 1 year after transplant	1 year after transplant	Kaplan-Meier method will be used to estimate the PFS
Progression free survival at 2 years after transplant	2 years after transplant	Kaplan-Meier method will be used to estimate the PFS
Progression free survival at 3 years after transplant	3 years after transplant	Kaplan-Meier method will be used to estimate the PFS
Non-relapse mortality at 2 years after transplant	2 years after transplant
Non-relapse mortality at 3 years after transplant	3 years after transplant
Overall survival(OS) at 1 year after transplant	1 year after transplant	Kaplan-Meier method will be used to estimate the OS
Overall survival at 3 years after transplant	3 years after transplant	Kaplan-Meier method will be used to estimate the OS
Graft versus host disease relapse free survival at 1 year after transplant	1 year after transplant
Graft versus host disease relapse free survival at 2 years after transplant	2 years after transplant
Graft versus host disease relapse free survival at 3 years after transplant	3 years after transplant
Relapse at 1 year after transplant.	1 year after transplant.
Relapse at 2 years after transplant.	2 years after transplant.
Non-relapse mortality at 1 year after transplant	1 year after transplant
Rate of grade III-IV Acute Graft Versus Host Disease (aGVHD) at 30 days after transplant	30 days after transplant
Overall survival at 2 years after transplant	2 years after transplant	Kaplan-Meier method will be used to estimate the OS
Relapse at 3 years after transplant.	3 years after transplant.
Rate of grade III-IV aGVHD at 100 days after transplant	100 days after transplant
Rate of grade III-IV aGVHD at 1 year after transplant	1 year after transplant
Rate of grade III-IV aGVHD at 2 years after transplant	2 years after transplant
Rate of grade III-IV aGVHD at 6 months after transplant	6 months after transplant
Rate of grade III-IV aGVHD at 3 years after transplant	3 years after transplant
Rate of grade II-IV aGVHD at 30 days after transplant	30 days after transplant
Rate of grade II-IV aGVHD at 100 days after transplant	100 days after transplant
Rate of grade II-IV aGVHD at 6 months after transplant	6 months after transplant
Rate of grade II-IV aGVHD at 1 year after transplant	1 year after transplant
Rate of grade II-IV aGVHD at 2 years after transplant	2 years after transplant
Rate of grade II-IV aGVHD at 3 years after transplant	3 years after transplant
Rate of severe Chronic Graft Versus Host Disease (cGVHD) at 100 days after transplant.	100 days after transplant
Rate of severe cGVHD at 6 months after transplant.	6 months after transplant
Rate of severe cGVHD at 1 year after transplant.	1 year after transplant
Rate of severe cGVHD at 2 years after transplant.	2 years after transplant
Rate of severe cGVHD at 3 years after transplant.	3 years after transplant
Rate of moderate cGVHD at 100 days after transplant	100 days after transplant
Rate of moderate cGVHD at 6 months after transplant	6 months after transplant
Rate of moderate cGVHD at 1 year after transplant	1 year after transplant
Rate of moderate cGVHD at 2 years after transplant	2 years after transplant
Rate of moderate cGVHD at 3 years after transplant	3 years after transplant
Rate of mild cGVHD at 100 days after transplant	100 days after transplant
Rate of mild cGVHD at 6 months after transplant	6 months after transplant
Rate of mild cGVHD at 1 year after transplant	1 year after transplant
Rate of mild cGVHD at 2 years after transplant	2 years after transplant
Rate of mild cGVHD at 3 years after transplant	3 years after transplant
Rate of serious infections at 1 year after transplant	1 year after transplant
Time to neutrophil engraftment.	60 days post treatment	Neutrophil engraftment will be calculated as the days from transplant where the absolute neutrophil count (ANC) reaches \>500cells/ul x 3 days.
Time to platelet engraftment.	60 days post treatment	Platelet engraftment will be calculated as the days from transplant where the platelet count reaches 20,000 platelets /ul without the need of transfusion of platelets for 7 days.

Trial Locations

Locations (1)

Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center Seidman Cancer Center; 🇺🇸 Cleveland, Ohio, United States