NCT04013685Active, not recruitingPhase 1
A Phase Ib Trial of Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With Either Orca-T, a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells, or Standard-of-Care Allogeneic Graft
Orca Biosystems, Inc.21 sites in 1 country155 target enrollmentStarted: November 21, 2019Last updated:
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Orca Biosystems, Inc.
- Enrollment
- 155
- Locations
- 21
- Primary Endpoint
- The incidence of primary graft failure
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Recipients must meet all of the following criteria:
- •Patients must be diagnosed with 1 of the following histopathologically confirmed diseases, for which a myeloablative hematopoietic stem cell transplant (HCT) is planned:
- •A) Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia who are not in CR or CRi (active disease) and/or MDS with >10% to <20% bone marrow blast burden (ages 18 to 75 years)
- •B) Acute leukemia in CR/CRi or MDS that is DRI intermediate to high risk (ages 66 to 75 years)
- •C) BPDCN (ages 18 to 65 years)
- •D) Participants aged 18 to 65 who would be eligible for the Phase 3 component of Precision-T except for mild impairments of renal and/or hepatic function as defined by an eGFR of 50 to <60 mL/min and/or a total bilirubin of >ULN to ≤2 x ULN and diagnosed with either of the following:
- •i. Acute myeloid, lymphoid, or mixed phenotype/undifferentiated leukemia that is in CR/CRi and DRI intermediate to high risk
- •a) MDS that is DRI intermediate to high risk
- •E) Acute or chronic leukemia in remission that is DRI low risk (ages 18 to 65 years), including the following:
- •i. CML in chronic phase but with a history of accelerated phase or blast crisis or who are resistant to or intolerant of more than 1 first- and second-generation tyrosine kinase inhibitors
- •ii. Acute myeloid leukemia (AML) with inv(16) without accompanying complex cytogenetics
- •Patients must be matched to a 8/8 HLA-matched related or unrelated donor
- •Estimated glomerular filtration rate (eGFR) >50 mL/minute
- •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 where hemolysis has been excluded) and ALT/AST <3 times ULN
Exclusion Criteria
- •Recipients meeting any of the following exclusion criteria will not be eligible:
- •History of 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.
- •Pre-planned donor lymphocyte infusion (DLI)
- •Planned pharmaceutical in vivo or ex vivo T cell depletion
- •Positive for anti-donor HLA antibodies against an allele in the selected donor
- •Karnofsky performance score <70%
- •Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) >4
- •Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
- •Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody
- •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
- •Women who are pregnant or breastfeeding
Arms & Interventions
Subjects with Acute Leukemia or Myelodysplastic Syndrome, or BPDCN
Experimental
This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.
Intervention: Orca-T (Biological)
Outcomes
Primary Outcomes
The incidence of primary graft failure
Time Frame: 365 days
The incidence of primary graft failure
The incidence of grade 3 or 4 aGVHD
Time Frame: 180 days
The incidence of grade 3 or 4 aGVHD
Secondary Outcomes
- 1 year graft-versus-host-disease-free and relapse-free survival (GRFS)(365 days)
- 1-year overall survival (OS)(365 days)
- incidence and severity of acute and chronic graft vs host disease (GvHD)(365 days)
- incidence of serious infections(365 days)
- incidence of engraftment(28 days)
Investigators
Study Sites (21)
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