ABBA CORD: dCBT w/ Abatacept for aGVHD Prophylaxis
- Conditions
- Interventions
- Registration Number
- NCT06680661
- Lead Sponsor
- Leland Metheny
- Brief Summary
The goal of this clinical trial is to see if adding abatacept to tacrolimus and MMF prevents or reduces the chances of acute graft versus host disease which is a complication that can occur after transplant in participants with blood cancer. The usual therapy for graft versus host disease prevention after a cord blood transplant includes tacrolimus and MMF. ...
- Detailed Description
Cord blood (CB) is a valuable alternative graft source 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. CB allows for greater HLA difference between d...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 20
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Patients with the following hematologic malignancies:
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Acute myelogenous leukemia (AML): High-risk and intermediate-risk AML including:
- Antecedent hematological disease (e.g., myelodysplasia (MDS))
- Treatment-related leukemia
- Complete Remission (CR1) with poor or intermediate-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23, del 5, del 7, complex cytogenetics)
- CR2 or CR3
- Induction failure or 1st relapse with < 10% blasts in the marrow
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Acute lymphoblastic leukemia (ALL):
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High-risk CR1 including:
- Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22)or 11q23 rearrangements)
- Philadelphia chromosome-like ALL
- Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy
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No CR within 4 weeks of initial treatment
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Induction failure with < 10% blasts in the marrow
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CR2 or CR3
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Myelodysplastic syndromes (MDS), Intermediate, High or Very High Risk by the revised international prognostic scoring system or treatment related MDS.
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Bi-phenotypic or mixed-phenotypic acute leukemia in:
- CR.
- Induction failure or 1st relapse with < 10% blasts in the marrow.
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Chronic Myelogenous Leukemia (CML) in second chronic phase after accelerated or blast crisis.
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Chronic Myelomonocytic Leukemia (CMML)
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Age > or equal to 18 years, < or equal to 65yrs
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KPS > or equal to 80
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Patients without a suitable HLA-matched related or unrelated donor
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Patient with the following CB units:
- At least two 4-8/8 HLA high resolution matched CB units. Both must have a cell dose of 1.5x107 TNC/kg each and 1.5x105 CD34+/kg
- A minimum of 1 CB unit as back up.
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Concurrent Therapy for Extramedullary Leukemia or CNS Lymphoma: Concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated. Such treatment may continue until the planned course is completed. Subjects 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.
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Subjects must have the ability to understand and the willingness to sign a written informed consent document.
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Patients with inadequate Organ Function as defined by:
- Creatinine clearance < 50ml/min
- 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% normal
- Cardiac: left ventricular ejection fraction < 50
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Patients 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.
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Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with RIC have the significant potential for teratogenic or abortifacient effects.
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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.
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Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
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Presence of donor-specific antibodies against chosen graft source.
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Hematopoietic Cell Transplantation Comorbidity index (HCT-CI) > 5.
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Prior autologous stem cell transplant within the preceding 12 months or prior allogeneic transplant.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Cyclophosphamide Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered. Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Fludarabine Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered. Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Thiotepa Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered. Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Total Body Irradiation Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered. Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Double Umbilical Cord Transplant Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered. Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Tacrolimus Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered. Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Mycophenolate Mofetil Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered. Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept Abatacept Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered.
- Primary Outcome Measures
Name Time Method Severe aGVDH free survival 180 days after treatment To assess severe aGVDH (grade III-IV acute GVHD) free survival (SGFS) at T+180.
- Secondary Outcome Measures
Name Time Method Non-relapse mortality 1 year post transplant Treatment Related Mortality (TRM) at 1 year is the percentage of patients who expire from treatment related toxicity attributed to transplant up to 1 year after transplant.
Overall Survival 1 year post transplant Overall Survival (OS) at 1 year is the percentage of patients alive at 1 year after transplant.
Rate of relapse 1 year post transplant Relapse incidence at 1 year is the percentage of patients who experience relapse of their hematologic malignancy up to 1 year after transplant.
Disease free survival 1 year post transplant Disease Free Survival at 1 year is the percentage of patients alive and without evidence of hematologic malignancy at 1 year after transplant.
Incidence of chronic GVHD 3 years post transplant Chronic graft versus host disease (cGVHD) 3-year cumulative incidence is the percentage of patients who experienced any cGVHD up to 3 years after transplant.
Rate of Grade III-IV aGVHD 180 days after treatment Grade III-IV aGVHD prevalence at T+180 is the percentage of patients who have grade III-IV aGVHD at T+180.
Rate of Grade II-IV aGVHD 180 days after treatment Grade II-IV aGVHD prevalence at T+180 is the percentage of patients who have grade II-IV aGVHD at T+180.
CMV reactivation rate 1 year after transplant The cumulative incidence of CMV reactivation at 1 year is defined as the detection of CMV within any organ by biopsy or within the plasma within the first year of transplant.
EBV reactivation rate 1 year after treatment The cumulative incidence of EBV reactivation at 1 year is defined as the detection of EBV in the plasma or blood less than 1000 copies/ml within the first year of transplant.
Time to neutrophil engraftment Within first 30 days of transplant 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 Within first 60 days of transplant 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.
Donor chimerism 1 year post transplant Donor chimerism rates will drawn 1 year post transplant.
Time to taper off tacrolimus Within 1 year of transplant The average time to taper off of tacrolimus will be calculated.
Time to taper off MMF Within 90 days of transplant The average time to taper off of mycophenolate mofetil (MMF) will be calculated.
Assessment of aGVDH biomarker ST2 28 days post transplant An assessment of aGVDH biomarker ST2 will occur 28 days post-transplant.
Assessment of aGVDH biomarker REG3α 28 days post transplant An assessment of aGVDH biomarker REG3α will occur 28 days post-transplant.
Trial Locations
- Locations (1)
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States