A Study of Engineered Donor Grafts (Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
A Study of Engineered Donor Grafts (Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
This study will evaluate the safety, tolerability, and efficacy of an engineered donor graft
("Orca-T", a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and
Regulatory T Cells) in participants undergoing myeloablative allogeneic hematopoietic cell
transplant transplantation for hematologic malignancies.
("Orca-T", a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and
Regulatory T Cells) in participants undergoing myeloablative allogeneic hematopoietic cell
transplant transplantation for hematologic malignancies.
Leukemia,
Myelodysplastic Syndrome,
Phase I
Phase I
Adults
Bone Marrow/Stem Cell Transplant
TregGraft
Dholaria, Bhagirathbhai
International
Vanderbilt University
07-16-2021
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Key Inclusion Criteria: Recipients must meet all of the following criteria: 1. 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] 2. Patients must be matched to a 8/8 HLA-matched related or unrelated donor 3. Estimated glomerular filtration rate (eGFR) > 50 mL/minute 4. Cardiac ejection fraction at rest 45% or shortening fraction of 27% by echocardiogram or radionuclide scan (MUGA) 5. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) 50% 6. 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: 1. History of prior allogeneic HCT 2. Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed. 3. Pre-planned donor lymphocyte infusion (DLI) 4. Planned pharmaceutical in vivo or ex vivo T cell depletion 5. Positive for anti-donor HLA antibodies against an allele in the selected donor 6. Karnofsky performance score 70% 7. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment 9. Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody 10. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment 11. Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected 12. Women who are pregnant or breastfeeding
Key Inclusion Criteria: Recipients must meet all of the following criteria: 1. 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] 2. Patients must be matched to a 8/8 HLA-matched related or unrelated donor 3. Estimated glomerular filtration rate (eGFR) > 50 mL/minute 4. Cardiac ejection fraction at rest 45% or shortening fraction of 27% by echocardiogram or radionuclide scan (MUGA) 5. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) 50% 6. 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: 1. History of prior allogeneic HCT 2. Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed. 3. Pre-planned donor lymphocyte infusion (DLI) 4. Planned pharmaceutical in vivo or ex vivo T cell depletion 5. Positive for anti-donor HLA antibodies against an allele in the selected donor 6. Karnofsky performance score 70% 7. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment 9. Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody 10. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment 11. Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected 12. Women who are pregnant or breastfeeding
