A Study of Engineered Donor Grafts (Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring hematopoietic stem cell transplantation, acute leukemia, Myelodysplastic syndromes, matched related donor, matched unrelated donor
Eligibility Criteria
Key Inclusion Criteria:
Recipients must meet all of the following criteria:
Patients must diagnosed with one of the following histopathologically confirmed diseases, for which a myeloablative hematopoietic stem cell transplant (HCT) is planned:
- acute myeloid, lymphoid or mixed phenotype leukemia that is not in CR/CRi [Ages 18-65]
- myelodysplastic syndromes with > 10% to < 20% bone marrow blast burden [Ages 18-65]
- acute myeloid, lymphoid or mixed phenotype leukemia that is in CR/CRi but is categorized as DRI very high risk [Ages 18-65]
- Myelofibrosis [Ages 18-65]
- Blastic Plasmacytoid Dendritic Cell Neoplasm [Ages 18-65]
- acute myeloid, lymphoid, mixed phenotype leukemia or myelodysplastic syndromes (therapy-related/secondary MDS or eligible for alloHCT per 2017 International Expert Panel) that are in CR and intermediate to high risk per the DRI in patients aged 66 to 75 [Ages 66-75]
- chronic myeloid leukemia that is in chronic phase with history of blast crisis or accelerated phase and/or is resistant to or intolerant of >1 first- or second-generation TKI [Ages 18-65]
- Patients must be matched to a 8/8 HLA-matched related or unrelated donor
- Estimated glomerular filtration rate (eGFR) > 50 mL/minute
- Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
- Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
- Total bilirubin < 2 times upper limit of normal (ULN) (patients with Gilbert's syndrome may be included where hemolysis has been excluded) and ALT/AST < 3 times ULN
Key Exclusion Criteria:
Recipients meeting any of the following exclusion criteria will not be eligible:
- History of prior allogeneic HCT
- Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
- Pre-planned donor lymphocyte infusion (DLI)
- Planned pharmaceutical in vivo or ex vivo T cell depletion
- Positive for anti-donor HLA antibodies against an allele in the selected donor
- Karnofsky performance score < 70%
- Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4
- Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
- Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody
- Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
- Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
- Women who are pregnant or breastfeeding
Sites / Locations
- City of HopeRecruiting
- Ronald Reagan UCLA Medical CenterRecruiting
- UC DavisRecruiting
- Stanford Health CareRecruiting
- Colorado Blood Cancer InstituteRecruiting
- University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer CenterRecruiting
- Moffitt Cancer CenterRecruiting
- Winship Cancer Institute - Emory UniversityRecruiting
- University of ChicagoRecruiting
- The University of Kansas Hospital
- MassachusettsRecruiting
- University of Michigan Health System - Michigan MedicineRecruiting
- Weill Cornell Medicine - New York-Presbyterian HospitalRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- Cleveland ClinicRecruiting
- OU Health Stephenson Cancer CenterRecruiting
- Oregon Health & Sciences University - Knight Cancer InstituteRecruiting
- Sarah Cannon Research InstituteRecruiting
- Vanderbilt UniversityRecruiting
- University of Texas MD Anderson Cancer Center
- Texas Transplant Institute
- University of Utah - Huntsman Cancer InstituteRecruiting
Arms of the Study
Arm 1
Experimental
Subjects with Acute Leukemia or Myelodysplasic Syndrome, Myelofibrosis, or BPDCN
This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.