Precision-T: A Randomized Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

This study will evaluate the safety, tolerability, and efficacy of Orca-T, an allogeneic stem cell and T-cell immunotherapy biologic manufactured for each patient (transplant recipient) from the mobilized peripheral blood of a specific, unique donor. It is composed of purified hematopoietic stem and progenitor cells (HSPCs), purified regulatory T cells (Tregs), and conventional T cells (Tcons) in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.

This posting represents the Phase III component of Precision-T. The Precision-T Ph1b component is described under NCT04013685.

Cross reference NCT04013685

Eligibility Criteria:
Key Inclusion Criteria:

* Matched to a related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and DRB1
* Diagnosed with one of the following diseases:

  * Acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), with or without the presence of known minimal residual disease
  * Myelodysplastic syndromes (MDS) that are indicated for alloHSCT per 2017 International Expert Panel recommendations and/or have therapy-related/secondary MDS, with ≤ 10% blast burden in the bone marrow
* Planned to undergo MA-alloHCT including one of the following myeloablative conditioning regimens:

  * TBI/Cy
  * TBI/Etoposide
  * BFT
* 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%
* Negative serum or urine beta-HCG test in females of childbearing potential
* ALT/AST \< 3 times ULN
* Recipients in screening must screen negative for SARS-CoV-2 RNA using a PCR-based test
* Disease Risk Index (DRI) overall risk categorization of intermediate or high
* Total bilirubin ≤ upper limit of normal (ULN)
* Estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute

Key Exclusion Criteria:

* 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.
* Planned donor lymphocyte infusion (DLI)
* Planned pharmaceutical in vivo or ex vivo T cell depletion
* Recipient positive anti-donor HLA antibodies against a mismatched allele in the selected donor
* Karnofsky performance score \< 70%
* Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) \> 4
* Uncontrolled bacterial, viral or fungal infections at time of enrollment
* Seropositive for HIV-1 or -2, HTLV-1 or -2, Hepatitis B sAg, Hepatitis C antibody
* Known allergy or hypersensitivity to, or intolerance of, tacrolimus
* Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal or Streptomyces avidinii proteins
* 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
* Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
* Women who are pregnant or breastfeeding
* Women of childbearing potential (WOCBP) or men who have sexual contact with WOCBP unwilling to use effective forms of birth control or abstinence for one year after transplantation