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A Study of Engineered Donor Grafts (Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Myelodysplastic Syndromes

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Orca-T (formerly TregGraft)
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

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

    • acute myeloid, lymphoid or mixed phenotype leukemia that is not in CR/CRi [Ages 18-65]
    • myelodysplastic syndromes with > 10% to < 20% bone marrow blast burden [Ages 18-65]
    • acute myeloid, lymphoid or mixed phenotype leukemia that is in CR/CRi but is categorized as DRI very high risk [Ages 18-65]
    • Myelofibrosis [Ages 18-65]
    • Blastic Plasmacytoid Dendritic Cell Neoplasm [Ages 18-65]
    • acute myeloid, lymphoid, mixed phenotype leukemia or myelodysplastic syndromes (therapy-related/secondary MDS or eligible for alloHCT per 2017 International Expert Panel) that are in CR and intermediate to high risk per the DRI in patients aged 66 to 75 [Ages 66-75]
    • chronic myeloid leukemia that is in chronic phase with history of blast crisis or accelerated phase and/or is resistant to or intolerant of >1 first- or second-generation TKI [Ages 18-65]
  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

Sites / Locations

  • City of HopeRecruiting
  • Ronald Reagan 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
  • The University of Kansas Hospital
  • MassachusettsRecruiting
  • 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
  • Sarah Cannon Research InstituteRecruiting
  • Vanderbilt UniversityRecruiting
  • University of Texas MD Anderson Cancer Center
  • Texas Transplant Institute
  • University of Utah - Huntsman Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Subjects with Acute Leukemia or Myelodysplasic Syndrome, Myelofibrosis, or BPDCN

Arm Description

This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.

Outcomes

Primary Outcome Measures

TregGraft (Orca-T), with single agent GVHD prophylaxis

Secondary Outcome Measures

1-year overall survival (OS)
1-year overall survival (OS)
1 year graft-versus-host-disease-free and relapse-free survival (GRFS)
1 year graft-versus-host-disease-free and relapse-free survival (GRFS)
incidence and severity of acute and chronic graft vs host disease (GvHD)
incidence and severity of acute and chronic graft vs host disease (GvHD)
incidence of serious infections
incidence of serious infections
incidence and timing of engraftment
incidence and timing of engraftment of platelets and neutrophils

Full Information

First Posted
July 3, 2019
Last Updated
September 23, 2023
Sponsor
Orca Biosystems, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04013685
Brief Title
A Study of Engineered Donor Grafts (Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
Official Title
A Multicenter Phase Ib Trial of Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With Orca-T (Formerly TregGraft), a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 21, 2019 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 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 evaluate the safety, tolerability, and efficacy of an engineered donor graft ("Orca-T", a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells) in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.

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, Myelodysplastic Syndromes, Acute Leukemia, Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), Chronic Myeloid Leukemia, Chronic Phase
Keywords
hematopoietic stem cell transplantation, acute leukemia, Myelodysplastic syndromes, matched related donor, matched unrelated donor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
255 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Subjects with Acute Leukemia or Myelodysplasic Syndrome, Myelofibrosis, or BPDCN
Arm Type
Experimental
Arm Description
This is a non-randomized, single-arm study. All enrolled subjects will receive an allogeneic HCT with the Orca-T product.
Intervention Type
Biological
Intervention Name(s)
Orca-T (formerly TregGraft)
Intervention Description
engineered donor allograft
Primary Outcome Measure Information:
Title
TregGraft (Orca-T), with single agent GVHD prophylaxis
Time Frame
365 days
Secondary Outcome Measure Information:
Title
1-year overall survival (OS)
Description
1-year overall survival (OS)
Time Frame
365 days
Title
1 year graft-versus-host-disease-free and relapse-free survival (GRFS)
Description
1 year graft-versus-host-disease-free and relapse-free survival (GRFS)
Time Frame
365 days
Title
incidence and severity of acute and chronic graft vs host disease (GvHD)
Description
incidence and severity of acute and chronic graft vs host disease (GvHD)
Time Frame
365 days
Title
incidence of serious infections
Description
incidence of serious infections
Time Frame
365 days
Title
incidence and timing of engraftment
Description
incidence and timing of engraftment of platelets and neutrophils
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Recipients must meet all of the following criteria: Patients must diagnosed with one of the following histopathologically confirmed diseases, for which a myeloablative hematopoietic stem cell transplant (HCT) is planned: acute myeloid, lymphoid or mixed phenotype leukemia that is not in CR/CRi [Ages 18-65] myelodysplastic syndromes with > 10% to < 20% bone marrow blast burden [Ages 18-65] acute myeloid, lymphoid or mixed phenotype leukemia that is in CR/CRi but is categorized as DRI very high risk [Ages 18-65] Myelofibrosis [Ages 18-65] Blastic Plasmacytoid Dendritic Cell Neoplasm [Ages 18-65] acute myeloid, lymphoid, mixed phenotype leukemia or myelodysplastic syndromes (therapy-related/secondary MDS or eligible for alloHCT per 2017 International Expert Panel) that are in CR and intermediate to high risk per the DRI in patients aged 66 to 75 [Ages 66-75] chronic myeloid leukemia that is in chronic phase with history of blast crisis or accelerated phase and/or is resistant to or intolerant of >1 first- or second-generation TKI [Ages 18-65] Patients must be matched to a 8/8 HLA-matched related or unrelated donor Estimated glomerular filtration rate (eGFR) > 50 mL/minute 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% 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: History of 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. Pre-planned donor lymphocyte infusion (DLI) Planned pharmaceutical in vivo or ex vivo T cell depletion Positive for anti-donor HLA antibodies against an allele in the selected donor Karnofsky performance score < 70% Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment Seropositive for HIV-1 or -2 antibody, HTLV-1 or -2 antibody, Hepatitis B sAg, or Hepatitis C antibody 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 Women who are pregnant or breastfeeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
James S McClellan, MD PhD
Phone
530-414-9743
Email
info@orcabiosystems.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 Reagan 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
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
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
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
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
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
Facility Name
The University of Kansas Hospital
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Massachusetts
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
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
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
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeremy Pantin
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
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Texas Transplant Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University of Utah - Huntsman Cancer Institute
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

12. IPD Sharing Statement

Learn more about this trial

A Study of Engineered Donor Grafts (Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

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