Clinical trial NCT06904482: Co-Transplant of an Unmodified Haplo-Identical Graft With Cord Blood
Official title: Co-Transplant of an Unmodified Haplo-Identical Graft With Cord Blood
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: aGVHD
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndromes
Keywords: Unmodified Haplo-Identical Graft with Cord Blood
post-transplant cyclophosphamide aGVHD prophylaxis
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2025-04-01
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression free survival(PFS) at 6 months after transplant
timeFrame: 6 months after transplant
Secondary outcomes:
measure: Progression free survival at 1 year after transplant
timeFrame: 1 year after transplant
measure: Progression free survival at 2 years after transplant
timeFrame: 2 years after transplant
measure: Progression free survival at 3 years after transplant
timeFrame: 3 years after transplant
measure: Non-relapse mortality at 1 year after transplant
timeFrame: 1 year after transplant
measure: Non-relapse mortality at 2 years after transplant
timeFrame: 2 years after transplant
measure: Non-relapse mortality at 3 years after transplant
timeFrame: 3 years after transplant
measure: Overall survival(OS) at 1 year after transplant
timeFrame: 1 year after transplant
measure: Overall survival at 2 years after transplant
timeFrame: 2 years after transplant
measure: Overall survival at 3 years after transplant
timeFrame: 3 years after transplant
measure: Graft versus host disease relapse free survival at 1 year after transplant
timeFrame: 1 year after transplant
measure: Graft versus host disease relapse free survival at 2 years after transplant
timeFrame: 2 years after transplant
measure: Graft versus host disease relapse free survival at 3 years after transplant
timeFrame: 3 years after transplant
measure: Relapse at 1 year after transplant.
timeFrame: 1 year after transplant.
measure: Relapse at 2 years after transplant.
timeFrame: 2 years after transplant.
measure: Relapse at 3 years after transplant.
timeFrame: 3 years after transplant.
measure: Rate of grade III-IV Acute Graft Versus Host Disease (aGVHD) at 30 days after transplant
timeFrame: 30 days after transplant
measure: Rate of grade III-IV aGVHD at 100 days after transplant
timeFrame: 100 days after transplant
measure: Rate of grade III-IV aGVHD at 6 months after transplant
timeFrame: 6 months after transplant
measure: Rate of grade III-IV aGVHD at 1 year after transplant
timeFrame: 1 year after transplant
measure: Rate of grade III-IV aGVHD at 2 years after transplant
timeFrame: 2 years after transplant
measure: Rate of grade III-IV aGVHD at 3 years after transplant
timeFrame: 3 years after transplant
measure: Rate of grade II-IV aGVHD at 30 days after transplant
timeFrame: 30 days after transplant
measure: Rate of grade II-IV aGVHD at 100 days after transplant
timeFrame: 100 days after transplant
measure: Rate of grade II-IV aGVHD at 6 months after transplant
timeFrame: 6 months after transplant
measure: Rate of grade II-IV aGVHD at 1 year after transplant
timeFrame: 1 year after transplant
measure: Rate of grade II-IV aGVHD at 2 years after transplant
timeFrame: 2 years after transplant
measure: Rate of grade II-IV aGVHD at 3 years after transplant
timeFrame: 3 years after transplant
measure: Rate of severe Chronic Graft Versus Host Disease (cGVHD) at 100 days after transplant.
timeFrame: 100 days after transplant
measure: Rate of severe cGVHD at 6 months after transplant.
timeFrame: 6 months after transplant
measure: Rate of severe cGVHD at 1 year after transplant.
timeFrame: 1 year after transplant
measure: Rate of severe cGVHD at 2 years after transplant.
timeFrame: 2 years after transplant
measure: Rate of severe cGVHD at 3 years after transplant.
timeFrame: 3 years after transplant
measure: Rate of moderate cGVHD at 100 days after transplant
timeFrame: 100 days after transplant
measure: Rate of moderate cGVHD at 6 months after transplant
timeFrame: 6 months after transplant
measure: Rate of moderate cGVHD at 1 year after transplant
timeFrame: 1 year after transplant
measure: Rate of moderate cGVHD at 2 years after transplant
timeFrame: 2 years after transplant
measure: Rate of moderate cGVHD at 3 years after transplant
timeFrame: 3 years after transplant
measure: Rate of mild cGVHD at 100 days after transplant
timeFrame: 100 days after transplant
measure: Rate of mild cGVHD at 6 months after transplant
timeFrame: 6 months after transplant
measure: Rate of mild cGVHD at 1 year after transplant
timeFrame: 1 year after transplant
measure: Rate of mild cGVHD at 2 years after transplant
timeFrame: 2 years after transplant
measure: Rate of mild cGVHD at 3 years after transplant
timeFrame: 3 years after transplant
measure: Rate of serious infections at 1 year after transplant
timeFrame: 1 year after transplant
measure: Time to neutrophil engraftment.
timeFrame: 60 days post treatment
measure: Time to platelet engraftment.
timeFrame: 60 days post treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center Seidman Cancer Center
state: Ohio
Study officials:
affiliation: Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center
name: Leland Metheny, MD
role: PRINCIPAL_INVESTIGATOR
References: