A Randomized Phase III 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-T

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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

Additional Trial Information

Phase 3

Enrollment: 174 patients (estimated)

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Published Results

Precision-Engineered Cell Therapy Orca-T Demonstrates High Relapse-Free Survival at 1 Year While Reducing Graft-Versus-Host Disease and Toxicity

November 15, 2022

Orca-T was successfully manufactured in a single, centralized GMP manufacturing facility, distributed throughout the U.S., and infused for all patients enrolled.

The relapse-free survival was 81% at both 1 year and 18 months in Orca-T recipients. MRD status was determined for 77 patients with acute leukemia by multicolor flow cytometry; of these patients, 31% were MRD+ when they received Orca-T. Amongst MRD- patients (n=53), RFS with Orca-T was 90% at both 1 year as compared to 66% in the CIBMTR cohort (n=324 MRD- patients). Amongst MRD+ patients (n=24), RFS was 68% at one year with Orca-T as compared to 48% in the comparator cohort (n=104).


Relapse prevention with Orca-T appeared to be enhanced further with a conditioning regimen consisting of busulfan, fludarabine, and thiotepa ("BFT", n=56 patients, median f/u 342 days); RFS was 90% at 12 months in this group. This included patients with MDS (n=6, 100% RFS at 1 yr), MRD+ acute leukemia (n=14, RFS 73% at 1 yr), MRD- acute leukemia (n=26, RFS 96% at 1 year), and acute leukemia with unknown MRD status (n=11, 91% RFS at 1 yr).


As with relapse, severe infections were low following Orca-T with 11% of patients developing Grade 3 infections per the BMT-CTN grading scale.


Median times to neutrophil and platelet engraftment were rapid with Orca-T at 13 and 16 days, respectively; graft failure was rare at 1.6%. Grade ≥ 3 aGVHD and mod/severe cGVHD rates were low with Orca-T at 5% and 6%, respectively, through 1 year post-transplant. Non-relapse mortality was low at 5% at 1 year; NRM with BFT was 0%. Overall, Orca-T shows GRFS of 76% and 69% at 1 year and 18 months post-transplant, respectively; OS was 91% and 86% at these time points post-transplant. No formal statistical comparison to the CIBMTR cohort was performed.

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

UCLA Medical Center of Hematology/Oncology

Los Angeles, CA

Open and Accepting

University of California Davis Comprehensive Cancer Center

Sacramento, CA

Open and Accepting

Stanford University Cancer Institute (Palo Alto)

Stanford, CA

Open and Accepting

Colorado

Colorado Blood Cancer Institute Sarah Cannon at Presbyterian/St. Luke's Medical Center (HealthONE)

Denver, CO

Open and Accepting

Florida

Sylvester Comprehensive Cancer Center (Main) University of Miami Health System

Miami, FL

Open and Accepting

Moffitt Cancer Center Magnolia Campus

Tampa, FL

Open and Accepting

Georgia

Winship Cancer Institute Emory University

Atlanta, GA

Open and Accepting

Illinois

University of Chicago Medicine Comprehensive Cancer Center

Chicago, IL

Open and Accepting

Massachusetts

Massachusetts General Hospital

Boston, MA

Open and Accepting

Michigan

University of Michigan Comprehensive Cancer Center Rogel Cancer Center

Ann Arbor, MI

Open and Accepting

New York

Memorial Sloan Kettering Cancer Center

New York, NY

Open and Accepting

Weill Cornell

New York, NY

Open and Accepting

Ohio

Cleveland Clinic - Taussig Cancer Center Taussig Cancer Institute

Cleveland, OH

Open and Accepting

Oklahoma

OU Health Stephenson Cancer Center

Oklahoma City, OK

Open and Accepting

Oregon

Oregon Health and Science University OHSU Knight Cancer Institute

Portland, OR

Open and Accepting

Tennessee

Vanderbilt-Ingram Cancer Center Henry-Joyce Cancer Clinic

Nashville, TN

Open and Accepting

Sarah Cannon Research Institute at Tennessee Oncology TriStar Centennial Medical Center

Nashville, TN

Open and Accepting

Utah

Huntsman Cancer Institute University of Utah

Salt Lake City, UT

Open and Accepting
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