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

Study Timeline

• Study First Submitted: 2022-03-30
• Study First Submitted QC: 2022-03-30
• Study First Posted: 2022-04-07
• Study Start: 2022-06-21
• Status Verified: 2024-04
• Last Update Submitted: 2024-05-24
• Last Update Posted: 2024-05-28
• Primary Completion: 2025-04
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 174

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

Read More

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

Read More

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
Chronic Graft-versus-Host-Disease-free Survival	Randomization through 730 days post transplant	An event for this time-to-event outcome is defined as death by any cause or moderate to severe cGVHD as defined by NIH consensus criteria, whichever is earlier.

Secondary Outcome Measures

Name	Time	Method
Time to moderate or severe cGVHD	Randomization through 730 days post transplant	An event for this time-to-event outcome is defined as time from randomization to the first onset of of moderate or severe cGVHD within 730 days after randomization. Death within 730 days after randomization without prior moderate or severe cGVHD is considered a competing event.
Overall Survival	730 days after end of enrollment	OS is defined as the time from randomization to death from any cause .
Graft-versus-Host Disease and Relapse-free survival (GRFS) up to 1 year	Day 0 through 365 days post-transplant	GRFS is defined as the time from randomization to death from any cause, relapse, the first onset of grade 3 or 4 aGVHD (graded per MAGIC criteria), or the first onset of moderate or severe cGVHD (graded per NIH consensus criteria), whichever is earliest.

Trial Locations

Locations (19)

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

University of Michigan Health System - Michigan Medicine; 🇺🇸 Ann Arbor, Michigan, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Winship Cancer Institute - Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

City of Hope; 🇺🇸 Duarte, California, United States

Ronald Reagan UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Weill Cornell Medicine - New York-Presbyterian Hospital; 🇺🇸 New York, New York, United States

Stanford Health Care; 🇺🇸 Stanford, California, United States

University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Oregon Health & Sciences University - Knight Cancer Institute; 🇺🇸 Portland, Oregon, United States

UC Davis; 🇺🇸 Sacramento, California, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States