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

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Mixed Phenotype Acute Leukemia

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Orca-T
Standard-of-Care
Sponsored by
Orca Biosystems, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring hematopoietic stem cell transplantation, acute leukemia, Myelodysplastic syndromes, matched related donor, matched unrelated donor, myelodysplastic syndrome

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of HopeRecruiting
  • Ronald Regan UCLA Medical CenterRecruiting
  • UC DavisRecruiting
  • Stanford Health CareRecruiting
  • Colorado Blood Cancer InstituteRecruiting
  • University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer CenterRecruiting
  • Moffitt Cancer CenterRecruiting
  • Winship Cancer Institute - Emory UniversityRecruiting
  • University of ChicagoRecruiting
  • Massachusetts General HospitalRecruiting
  • University of Michigan Health System - Michigan MedicineRecruiting
  • Weill Cornell Medicine - New York-Presbyterian HospitalRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Cleveland ClinicRecruiting
  • OU Health Stephenson Cancer CenterRecruiting
  • Oregon Health & Sciences University - Knight Cancer InstituteRecruiting
  • Vanderbilt UniversityRecruiting
  • Sarah Cannon Research InstituteRecruiting
  • University of UtahRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Orca-T

Standard of Care alloHCT Control

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

Chronic Graft-versus-Host-Disease-free Survival
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

Secondary Outcome Measures

Graft-versus-Host-Disease and Relapse-free survival (GRFS)
An event for this time-to-event outcome is defined as survival free of death from any cause, relapse, Grade 3-4 aGVHD (graded per MAGIC), and moderate to severe cGVHD (graded per NIH consensus criteria).
Moderate to severe chronic graft-versus-host-disease
An event for this time-to-event outcome is defined as moderate to severe cGVHD as defined by NIH consensus criteria.
Relapse-free survival
Survival free of death from relapse.

Full Information

First Posted
March 30, 2022
Last Updated
September 23, 2023
Sponsor
Orca Biosystems, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05316701
Brief Title
Precision-T: A Randomized Phase III Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
Acronym
Orca-T
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 21, 2022 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
April 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Orca Biosystems, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will compare the safety and efficacy between patients receiving an engineered donor graft ("Orca-T", a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells) or standard-of-care (SOC) control in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation (MA-alloHCT) 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Mixed Phenotype Acute Leukemia, Undifferentiated Leukemia, High-risk Myelodysplastic Syndrome, Acute Leukemia, Therapy-Related Myelodysplastic Syndrome, MDS
Keywords
hematopoietic stem cell transplantation, acute leukemia, Myelodysplastic syndromes, matched related donor, matched unrelated donor, myelodysplastic syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
The Phase III is a randomized, open-label, multicenter study comparing outcomes between patients receiving Orca-T followed by single-agent tacrolimus or standard-of-care (SOC) control followed by dual agent, tacrolimus-based Graft-versus-Host-Disease (GVHD) prophylaxis regimen
Masking
None (Open Label)
Allocation
Randomized
Enrollment
174 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Orca-T
Arm Type
Experimental
Arm Description
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).
Arm Title
Standard of Care alloHCT Control
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Orca-T
Other Intervention Name(s)
TregGraft
Intervention Description
engineered donor allograft
Intervention Type
Biological
Intervention Name(s)
Standard-of-Care
Other Intervention Name(s)
SOC
Intervention Description
unmanipulated donor allograft
Primary Outcome Measure Information:
Title
Chronic Graft-versus-Host-Disease-free Survival
Description
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
Time Frame
Randomization through 730 days post transplant
Secondary Outcome Measure Information:
Title
Graft-versus-Host-Disease and Relapse-free survival (GRFS)
Description
An event for this time-to-event outcome is defined as survival free of death from any cause, relapse, Grade 3-4 aGVHD (graded per MAGIC), and moderate to severe cGVHD (graded per NIH consensus criteria).
Time Frame
Day 0 through 365 days post-transplant
Title
Moderate to severe chronic graft-versus-host-disease
Description
An event for this time-to-event outcome is defined as moderate to severe cGVHD as defined by NIH consensus criteria.
Time Frame
Day 0 through 365 days post-transplant
Title
Relapse-free survival
Description
Survival free of death from relapse.
Time Frame
Day 0 through 730 days post-transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
James S McClellan, MD PhD
Phone
530 414 9743
Email
info@orcabio.com
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amandeep Salhotra
Facility Name
Ronald Regan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caspian Oliai, MD
First Name & Middle Initial & Last Name & Degree
Bruck Habtemariam
Email
BHabtemariam@mednet.ucla.edu
Facility Name
UC Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rasmus Hoeg
First Name & Middle Initial & Last Name & Degree
Dara Feleciano, RN MSN
Email
djfeleciano@ucdavis.edu
Facility Name
Stanford Health Care
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Everett Meyer, MD, PhD
First Name & Middle Initial & Last Name & Degree
Lindsay Danley
Email
lindsmd@stanford.edu
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alireza Eghtedar, MD
Phone
720-754-4800
Facility Name
University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio M Jimenez, MD
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rawan Faramand, MD
Phone
888-663-3488
Email
Rawan.Faramand@moffitt.org
Facility Name
Winship Cancer Institute - Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Edmund Waller, MD, PhD
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Satyajit Kosuri, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi-Bin Chen, MD
Phone
617-724-3456
Email
ychen6@partners.org
Facility Name
University of Michigan Health System - Michigan Medicine
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cancer Center Hotline
Phone
800-865-1125
First Name & Middle Initial & Last Name & Degree
John Magenau, MD
Facility Name
Weill Cornell Medicine - New York-Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra Gomez Arteaga, MD
First Name & Middle Initial & Last Name & Degree
Meredith Mullane, RN
Phone
212-746-0702
Email
Met9042@med.cornell.edu
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roni Tamari, MD
Email
abmttrials@mskcc.org
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Betty K Hamilton, MD
Phone
216-444-7923
Email
taussigresearch@ccf.org
Facility Name
OU Health Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Holter-Chakrabarty, MD
Phone
405-271-8299
First Name & Middle Initial & Last Name & Degree
Silas Day
Phone
(405) 271-8001
Ext
48748
Facility Name
Oregon Health & Sciences University - Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arpita Gandhi, MD
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bhagirathbhai Dholaria, MD
Phone
615-343-6653
First Name & Middle Initial & Last Name & Degree
Rohan Goel
Email
rohan.w.goel@vumc.org
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeremy Pantin, MD
Phone
615-342-3385
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sagar Patel, MD
First Name & Middle Initial & Last Name & Degree
Collind Boyington
Email
Collind.boyington@hci.utah.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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