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出境医 / 临床实验 / A Study of Engineered Donor Grafts (TregGraft/Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

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

Study Description
Brief Summary:
This study will evaluate the safety, tolerability, and efficacy of an engineered donor graft ("TregGraft"/"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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Lymphoid Leukemia Myelodysplastic Syndromes Acute Leukemia Biological: TregGraft (Orca-T) Phase 1

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase Ib Trial for Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With TregGraft (Orca-T), a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells
Actual Study Start Date : November 21, 2019
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : November 30, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Subjects with Acute Leukemia or Myelodysplasic Syndrome

This is a non-randomized, single-arm study. Patients will be grouped based on their underlying disease:

Group 1 will enroll subjects planning to undergo myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) for the treatment of either acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), and with no known minimal residual disease positivity.

Group 2 will enroll subjects Subjects planning to undergo MA-alloHCT for acute myeloid, lymphoid or mixed phenotype leukemia that is either:

  • not in morphologic CR with bone marrow infiltration by leukemic blasts of <= 10%, or
  • in morphologic CR with evidence of minimal residual positivity by either multiparameter flow cytometric analysis or by a nucleic acid-based technique.

Group 3 will enroll subjects planning to MA-alloHCT for high or very high risk myelodysplasic syndrome (MDS) myelodysplastic syndromes.

 Biological: TregGraft (Orca-T)
engineered donor allograft
Outcome Measures
Primary Outcome Measures :
  1. TregGraft (Orca-T), with single agent GVHD prophylaxis [ Time Frame: 365 days ]

Secondary Outcome Measures :
  1. 1-year overall survival (OS) [ Time Frame: 365 days ]
    1-year overall survival (OS)

  2. 1 year graft-versus-host-disease-free and relapse-free survival (GRFS) [ Time Frame: 365 days ]
    1 year graft-versus-host-disease-free and relapse-free survival (GRFS)

  3. incidence and severity of acute and chronic graft vs host disease (GvHD) [ Time Frame: 365 days ]
    incidence and severity of acute and chronic graft vs host disease (GvHD)

  4. incidence of serious infections [ Time Frame: 365 days ]
    incidence of serious infections

  5. incidence and timing of engraftment [ Time Frame: 28 days ]
    incidence and timing of engraftment of platelets and neutrophils


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
    • high or very high risk myelodysplastic syndromes
  2. Patients with active acute leukemia (i.e. not in morphologic complete response) must have bone marrow infiltration by leukemic blasts of <= 10%,
  3. Patients must be matched to a related or unrelated donor
  4. Estimated glomerular filtration rate (eGFR) > 50 mL/minute
  5. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
  6. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
  7. 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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: James S McClellan, MD PhD 1-530-414-9743 info@orcabiosystems.com

Locations
Layout table for location information
United States, California
Ronald Reagan UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: James S McClellan, MD PhD         
UC Davis Recruiting
Sacramento, California, United States, 95817
Contact: James S McClellan, MD PhD         
Stanford Health Care Recruiting
Stanford, California, United States, 94305
Contact: James S McClellan, MD, PhD         
United States, Kansas
The University of Kansas Hospital Recruiting
Kansas City, Kansas, United States, 66160
Contact: James S McClellan, MD, PhD         
United States, Oregon
Oregon Health & Sciences University - Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: James S McClellan, MD, PhD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: James S McClellan, MD PhD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77054
Contact: James S McClellan, MD PhD         
Sponsors and Collaborators
Orca Biosystems, Inc.
Tracking Information
First Submitted Date  ICMJE July 3, 2019
First Posted Date  ICMJE July 10, 2019
Last Update Posted Date December 4, 2020
Actual Study Start Date  ICMJE November 21, 2019
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2020) 		TregGraft (Orca-T), with single agent GVHD prophylaxis [ Time Frame: 365 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 8, 2019)
  • The incidence of primary graft failure [ Time Frame: From day of transplant ("Day 0") through day +28 post-transplant ]
    The incidence of primary graft failure
  • The incidence of Grade III-V acute graft-vs-host disease (GVHD) [ Time Frame: Day 0 through Day +100 ]
    The incidence of Grade III-V acute GVHD
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
  • 1-year overall survival (OS) [ Time Frame: 365 days ]
    1-year overall survival (OS)
  • 1 year graft-versus-host-disease-free and relapse-free survival (GRFS) [ Time Frame: 365 days ]
    1 year graft-versus-host-disease-free and relapse-free survival (GRFS)
  • incidence and severity of acute and chronic graft vs host disease (GvHD) [ Time Frame: 365 days ]
    incidence and severity of acute and chronic graft vs host disease (GvHD)
  • incidence of serious infections [ Time Frame: 365 days ]
    incidence of serious infections
  • incidence and timing of engraftment [ Time Frame: 28 days ]
    incidence and timing of engraftment of platelets and neutrophils
Original Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2019)
  • Timing of Neutrophil engraftment [ Time Frame: Day 0 through Day +28 ]
    Timing of Neutrophil engraftment
  • Timing of Platelet engraftment [ Time Frame: Day 0 through Day +28 ]
    Timing of Platelet engraftment
  • Incidence of secondary graft failure [ Time Frame: Day 0 through Day +100 ]
    Incidence of secondary graft failure
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Day 0 through Day +365 ]
    Incidence of treatment-emergent adverse events (TEAEs)
  • Incidence GVHD (all grades) [ Time Frame: Day 0 through Day +100 ]
    Incidence of acute GVHD (all grades)
  • Incidence of steroid-refractory acute GVHD, including Grade III-IV steroid-refractory acute GVHD [ Time Frame: Day 0 through Day +100 ]
    Incidence of steroid-refractory acute GVHD, including Grade III-IV steroid-refractory acute GVHD
  • Incidence of chronic GVHD [ Time Frame: Day 0 through Day +365 ]
    Incidence of chronic GVHD
  • Incidence of Post Transplant Lymphoproliferative Disorder (PTLD) [ Time Frame: Day 0 through Day +365 ]
    Incidence of Post Transplant Lymphoproliferative Disorder (PTLD)
  • Frequency of Non-relapse mortality (NRM) [ Time Frame: Day 0 through Day +365 ]
    Frequency of Non-relapse mortality (NRM)
  • Frequency of disease relapse (Arms I and III) [ Time Frame: Day 0 through Day +365 ]
    Frequency of disease relapse (Arms I and III)
  • GVHD-free and relapse-free survival (GRFS) [ Time Frame: Day 0 to Day +365 ]
    GVHD-free and relapse-free survival (GRFS)
  • 1-year overall survival (OS) [ Time Frame: Day 0 to Day +365 ]
    1-year overall survival (OS)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Engineered Donor Grafts (TregGraft/Orca-T) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
Official Title  ICMJE A Multicenter Phase Ib Trial for Patients With Advanced Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation With TregGraft (Orca-T), a T-cell-Depleted Graft With Additional Infusion of Conventional T Cells and Regulatory T Cells
Brief Summary This study will evaluate the safety, tolerability, and efficacy of an engineered donor graft ("TregGraft"/"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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Acute Lymphoid Leukemia
  • Myelodysplastic Syndromes
  • Acute Leukemia
Intervention  ICMJE Biological: TregGraft (Orca-T)
engineered donor allograft
Study Arms  ICMJE Experimental: Subjects with Acute Leukemia or Myelodysplasic Syndrome

This is a non-randomized, single-arm study. Patients will be grouped based on their underlying disease:

Group 1 will enroll subjects planning to undergo myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) for the treatment of either acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), and with no known minimal residual disease positivity.

Group 2 will enroll subjects Subjects planning to undergo MA-alloHCT for acute myeloid, lymphoid or mixed phenotype leukemia that is either:

  • not in morphologic CR with bone marrow infiltration by leukemic blasts of <= 10%, or
  • in morphologic CR with evidence of minimal residual positivity by either multiparameter flow cytometric analysis or by a nucleic acid-based technique.

Group 3 will enroll subjects planning to MA-alloHCT for high or very high risk myelodysplasic syndrome (MDS) myelodysplastic syndromes.

Intervention: Biological: TregGraft (Orca-T)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 8, 2019) 		84
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2022
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
    • high or very high risk myelodysplastic syndromes
  2. Patients with active acute leukemia (i.e. not in morphologic complete response) must have bone marrow infiltration by leukemic blasts of <= 10%,
  3. Patients must be matched to a related or unrelated donor
  4. Estimated glomerular filtration rate (eGFR) > 50 mL/minute
  5. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
  6. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
  7. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: James S McClellan, MD PhD 1-530-414-9743 info@orcabiosystems.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04013685
Other Study ID Numbers  ICMJE TRGFT-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Orca Biosystems, Inc.
Study Sponsor  ICMJE Orca Biosystems, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Orca Biosystems, Inc.
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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