What's the purpose of this trial?
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.
This trial is currently open and accepting patients.
What will happen during the trial?
You may be able to join this trial if you:
The following criteria is a partial list of reasons why patients may be
eligible to participate in this clinical trial. Further evaluation with a medical professional is
required.
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
Additional Trial Information
Phase 1
Enrollment: 255 patients (estimated)
View More
