Phase I Trial for Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation From an HLA-Mismatched Donor (7/8) With Orca-T
The study goal is to characterize the safety of the combination of Orca-T with dual agent GVHD prophylaxis.
• Eligible diseases:
‣ Acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi) as defined in Section 6.1.3; with or without the presence of known minimal residual disease, or
⁃ Myelodysplasic syndrome (MDS) myelodysplastic syndromes eligible for alloHSCT and/or treatment-related MDS \<10% blasts
• Age ≥ 18 and ≤ 70 years at the time of enrollment.
• Eligible for myeloablative alloHCT including one of two the myeloablative conditioning regimens (fractionated total body irradiation plus cyclophosphamide or busulfan, fludarabine, and thiotepa)
• Has a related or unrelated donor available who is 7/8 match (single allele mismatched) at HLA-A, -B, -C, and -DRB1, all typed using DNA-based high-resolution methods.
• Estimated glomerular filtration rate (eGFR) ≥ 50 mL/minute or creatinine \< 2 mg/dL.
• 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 once hemolysis has been excluded).
• Ability to understand and the willingness to provide written informed consent.
⁃ Negative serum or urine beta-HCG test in females of childbearing potential (FCBP) within 3 weeks of enrollment.
⁃ A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
⁃ Able to give informed consent. Legal authorized representative (LAR) is permitted if subject is cognitively able to provide verbal assent.
⁃ Karnofsky Performance Score ≥70%