Clinical trial NCT04013685: Precision-T: A Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Acute Lymphoid Leukemia
Myelodysplastic Syndromes
Acute Leukemia
Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Chronic Myeloid Leukemia
Keywords: hematopoietic stem cell transplantation
acute leukemia
Myelodysplastic syndromes
matched related donor
matched unrelated donor
Lead sponsor: Orca Biosystems, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-10
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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:

   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
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

Primary outcomes:
measure: The incidence of primary graft failure
timeFrame: 365 days
measure: The incidence of grade 3 or 4 aGVHD
timeFrame: 180 days
Secondary outcomes:
measure: 1-year overall survival (OS)
timeFrame: 365 days
measure: 1 year graft-versus-host-disease-free and relapse-free survival (GRFS)
timeFrame: 365 days
measure: incidence and severity of acute and chronic graft vs host disease (GvHD)
timeFrame: 365 days
measure: incidence of serious infections
timeFrame: 365 days
measure: incidence of engraftment
timeFrame: 28 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Miami
country: United States
facility: University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute - Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Boston
country: United States
facility: Massachusetts
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System - Michigan Medicine
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medicine - New York-Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Sciences University - Knight Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Institute
state: Utah
Study officials:
References: