precision-t: a randomized study of orca-t in recipients undergoing allogeneic transplantation for hematologic malignancies

Conditions: Acute Myeloid Leukemia; Acute Lymphoid Leukemia; Mixed Phenotype Acute Leukemia; Undifferentiated Leukemia; Myelodysplastic Syndrome; Acute Leukemia; Therapy-Related Myelodysplastic Syndrome

Summary: 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

Keywords: hematopoietic stem cell transplantation acute leukemia myelodysplastic syndromes matched related donor matched unrelated donor myelodysplastic syndrome