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

Phase 3

Active, not recruiting

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

Interventions: Biological: Orca-T
Biological: Standard-of-Care

Registration Number: NCT05316701

Lead Sponsor: Orca Biosystems, Inc.

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.

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

Detailed Description: Cross reference NCT04013685

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 187

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Orca-T	Orca-T	For patients randomized to the Orca-T arm, Orca-T will be administered after myeloablative conditioning regimen. Single-agent GVHD prophylaxis with tacrolimus will be administered following Tcon infusion (generally Day +3).
Standard of Care alloHCT Control	Standard-of-Care	For patients randomized to the standard-of-care control arm, an unmanipulated allograft derived from the peripheral blood of a matched donor will be administered after a myeloablative conditioning regimen. Dual-agent prophylaxis consisting of tacrolimus plus methotrexate will be administered starting on Day -3.

Primary Outcome Measures

Name	Time	Method
Event-free at 12 Months for Moderate or Severe Chronic Graft-versus-Host-Disease-free Survival (cGFS) Per Endpoint Adjudication Committee (EAC)	Day 0 through 730 days after transplantation	Event-free rate estimated at 12 months for cGFS per EAC, which is defined as the time from date of allogeneic hematopoietic cell transplantation (alloHCT) (ie, day 0) to date of death from any cause or first onset of moderate or severe chronic graft-versus-host disease (cGVHD) (graded per NIH consensus criteria), whichever was earliest, within 2 years after day 0. cGVHD was assessed and graded by EAC blinded to treatment assignment. Each participant in the study is followed for up to 730 days after transplant. Primary analysis was event driven (ie, when 56 participants had died or had moderate or severe cGVHD) and was not based on duration of follow-up. The analysis was conducted using all available data at the time that the 56th event occurred, and event-free rate at 12 months was estimated regardless of length of follow-up for individual participants. At the time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.

Secondary Outcome Measures

Name	Time	Method
Event Rate at 12 Months for Time to Moderate or Severe cGVHD Per EAC	Day 0 through 730 days after transplantation	Event rate estimated at 12 months for time from alloHCT to first onset of moderate or severe cGVHD defined by NIH consensus criteria within 2 years after day 0. Death within 2 years after day 0 without prior moderate or severe cGVHD was considered a competing event. cGVHD was assessed and graded by an independent EAC. Each participant in the study is followed for up to 730 days after transplant. The primary analysis was triggered by the 56th cGFS event (ie, when 56 participants had died or had moderate or severe chronic GVHD) and was not based on the duration of follow-up. Therefore, the analysis was conducted using all available data at the time that the 56th cGFS event occurred, and the event rate of moderate or severe cGVHD at 12 months was estimated regardless of the length of follow-up for individual participants. At the time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.
Event-free at 12 Months for Overall Survival (OS)	Up to 730 days after end of enrollment	Event-free rate estimated at 12 months for OS, which is defined as time from randomization to death from any cause. Each participant in the study is followed for up to 730 days after transplant. The analysis was triggered by the 56th cGFS event (ie, when 56 participants had died or had moderate or severe chronic GVHD) and was not based on the duration of follow-up. Therefore, the analysis was conducted using all available data at the time that the 56th cGFS event occurred, and the event-free rate of OS at 12 months was estimated regardless of the length of follow-up for individual participants. At the time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.
Event-free Rate at 12 Months for Graft-versus-host Disease-free and Relapse-free Survival (GRFS) Per EAC	Day 0 through 730 days after transplantation	Event-free rate estimated at 12 months for GRFS, which is defined as time from alloHCT to death from any cause, relapse, the first onset of grade 3 or 4 acute GVHD (graded per Mount Sinai aGVHD International Consortium \[MAGIC\] criteria), or the first onset of moderate or severe cGVHD (graded per NIH consensus criteria), whichever is earliest, within 2 years from day 0 as assessed by independent EAC. Each participant in the study is followed for up to 730 days after transplant. The analysis was triggered by the 56th cGFS event (ie, when 56 participants had died or had moderate or severe cGVHD) and not based on duration of follow-up. Therefore, analysis was conducted using all available data at the time that the 56th cGFS event occurred, and event-free rate of GRFS at 12 months was estimated regardless of length of follow-up for individual participants. At time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.

Trial Locations

Locations (19): City of Hope
🇺🇸
Duarte, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸
Los Angeles, California, United States
UC Davis
🇺🇸
Sacramento, California, United States
Stanford Health Care
🇺🇸
Stanford, California, United States
Colorado Blood Cancer Institute
🇺🇸
Denver, Colorado, United States
University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center
🇺🇸
Miami, Florida, United States
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Winship Cancer Institute - Emory University
🇺🇸
Atlanta, Georgia, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
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City of Hope
🇺🇸Duarte, California, United States