A Study of Engineered Donor Grafts (Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
- Interventional
- Recruiting
- NCT04013685
Contact Information
A Multicenter Phase Ib Trial of Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With Orca-T (Formerly TregGraft), a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells
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.
Gender
All
Age Group
18 Years to 75 Years
Accepting Healthy Volunteers?
No
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
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