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A Phase 1 Study of Engineered Donor Grafts (Orca-Q) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
OrcaGraft (Orca-Q)
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

Eligibility Criteria

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

Key Inclusion Criteria:

  1. Age ≥ 18 and ≤ 65 years at the time of enrollment
  2. Diagnosed acute myeloid, lymphoid or mixed phenotype leukemia, or high or very high risk myelodysplasic syndrome (MDS) or Myelofibrosis
  3. Planned to undergo myeloablative allogeneic hematopoietic stem cell transplant (HCT)
  4. Matched to a related or unrelated donor or to a haploidentical donor
  5. Estimated glomerular filtration rate (eGFR) > 50 mL/minute
  6. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
  7. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
  8. Total bilirubin < 1.5 times upper limit of normal (ULN) (< 3 times if attributed to Gilbert's syndrome) and ALT/AST < 3 times ULN

Key Exclusion Criteria:

  1. 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. Planned donor lymphocyte infusion (DLI)
  4. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor
  5. Karnofsky performance score < 70% (Appendix 12.7)
  6. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 (Appendix 12.8)
  7. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
  8. Seropositive for HIV-1 or -2, HTLV-1 or -2
  9. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
  10. Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
  11. History of idiopathic or secondary myelofibrosis
  12. Women who are pregnant or breastfeeding

Sites / Locations

  • City of HopeRecruiting
  • UC DavisRecruiting
  • Stanford Health CareRecruiting
  • Emory UniversityRecruiting
  • The University of Kansas HospitalRecruiting
  • Ohio State UniversityRecruiting
  • University of Texas MD Anderson Cancer CenterRecruiting
  • Froedtert Memorial Lutheran Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm A

Arm B

Arm C

Arm Description

Recipients with HLA-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor; with single-agent GVHD prophylaxis given

Recipients with haploidentical-related donors; with single-agent GVHD prophylaxis given

Recipients with an HLA-identical related or unrelated donor; no GVHD prophylaxis given

Outcomes

Primary Outcome Measures

Number of Dose Limiting Toxicities
Safety and tolerability of Orca-Q (formerly OrcaGraft) in adults undergoing myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) will be evaluated by identification of the following dose limiting toxicities: Grade ≥ 3 infusion-related reaction or cytokine release syndrome, Grade ≥ 3 acute GVHD, Any Grade ≥ 3 treatment-related non-hematologic event not clearly related to the underlying malignancy, intercurrent infection, the HCT conditioning regimen, or other pre-existing medical condition, and by instance of primary graft failure, defined as being alive without recovery of neutrophils during the evaluation period
Primary Graft failure through Day +28 (dose expansion)
Primary graft failure in the dose expansion phase, defined as being alive without recovery of neutrophils during the evaluation period

Secondary Outcome Measures

Neutrophil Engraftment through Day +28
Neutrophil engraftment defined as an absolute neutrophil count of >/=500/mm3 for 3 consecutive days
Platelet engraftment through Day +50
Platelet engraftment is defined as achieving a platelet count > 20,000/mm3 for 3 consecutive days without platelet transfusion in the preceding 7 days, by Day +50
Secondary graft failure through Day +100
Secondary graft failure is defined as neutrophil engraftment followed by subsequent decline in absolute neutrophil counts < 500 cells/μL, unresponsive to growth factor therapy, by Day +100
Treatment-emergent adverse events (TEAEs) through the safety reporting period
TEAEs categorized by System Organ Lass and graded according to the CTCAE v5.0
Acute GVHD through Day +100
Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria
Steroid-refractory acute GVHD through Day +100
Steroid-refractory acute GVHD will be defined as per the EBMT-NIH-CIBMTR Task Force position statement
Chronic GVHD through Day +365
Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria
Post-Transplant Lymphoproliferative Disorder (PTLD) through Day +365
PTLD is defined as a biopsy consistent with the 2017 World Health Organization (WHO) classification of PTLD
Incidence of non-relapse mortality (NRM) through Day +365
NRM is defined as death without evidence of disease recurrence
Incidence of disease relapse through Day +365
Recurrence of primary disease for transplant
GVHD-free and relapse-free survival (GRFS) through Day +365
Survival free from GVHD and relapse
Disease-free survival (DFS) through Day +365
Disease-free survival is the time from date of transplant to death or relapse, whichever comes first.
Overall survival through Day +365
OS is defined as the time from the date of transplant to the date of death from any cause or, for surviving patients, to the date of last follow-up.

Full Information

First Posted
January 10, 2019
Last Updated
March 21, 2023
Sponsor
Orca Biosystems, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03802695
Brief Title
A Phase 1 Study of Engineered Donor Grafts (Orca-Q) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
Official Title
A Phase 1, Dose Escalation and Expansion Study of Engineered Donor Grafts Derived From Mobilized Peripheral Blood (Orca-Q, Formerly OrcaGraft), With Single Agent Graft Versus-host Disease Prophylaxis, in Recipients Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 8, 2019 (Actual)
Primary Completion Date
April 1, 2024 (Anticipated)
Study Completion Date
April 1, 2026 (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

5. Study Description

Brief Summary
This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts ("OrcaGraft"/"Orca-Q") 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 Lymphoblastic Leukemia, Myelodysplastic Syndromes, Acute Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
186 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Recipients with HLA-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor; with single-agent GVHD prophylaxis given
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Recipients with haploidentical-related donors; with single-agent GVHD prophylaxis given
Arm Title
Arm C
Arm Type
Experimental
Arm Description
Recipients with an HLA-identical related or unrelated donor; no GVHD prophylaxis given
Intervention Type
Biological
Intervention Name(s)
OrcaGraft (Orca-Q)
Intervention Description
engineered donor allograft
Primary Outcome Measure Information:
Title
Number of Dose Limiting Toxicities
Description
Safety and tolerability of Orca-Q (formerly OrcaGraft) in adults undergoing myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) will be evaluated by identification of the following dose limiting toxicities: Grade ≥ 3 infusion-related reaction or cytokine release syndrome, Grade ≥ 3 acute GVHD, Any Grade ≥ 3 treatment-related non-hematologic event not clearly related to the underlying malignancy, intercurrent infection, the HCT conditioning regimen, or other pre-existing medical condition, and by instance of primary graft failure, defined as being alive without recovery of neutrophils during the evaluation period
Time Frame
28 Days after administration of Orca-Q/OrcaGraft
Title
Primary Graft failure through Day +28 (dose expansion)
Description
Primary graft failure in the dose expansion phase, defined as being alive without recovery of neutrophils during the evaluation period
Time Frame
28 Days after administration of Orca-Q/OrcaGraft
Secondary Outcome Measure Information:
Title
Neutrophil Engraftment through Day +28
Description
Neutrophil engraftment defined as an absolute neutrophil count of >/=500/mm3 for 3 consecutive days
Time Frame
28 days after administration of Orca-Q/OrcaGraft
Title
Platelet engraftment through Day +50
Description
Platelet engraftment is defined as achieving a platelet count > 20,000/mm3 for 3 consecutive days without platelet transfusion in the preceding 7 days, by Day +50
Time Frame
50 days after administration of Orca-Q/OrcaGraft
Title
Secondary graft failure through Day +100
Description
Secondary graft failure is defined as neutrophil engraftment followed by subsequent decline in absolute neutrophil counts < 500 cells/μL, unresponsive to growth factor therapy, by Day +100
Time Frame
100 days after administration of Orca-Q/OrcaGraft
Title
Treatment-emergent adverse events (TEAEs) through the safety reporting period
Description
TEAEs categorized by System Organ Lass and graded according to the CTCAE v5.0
Time Frame
100 days after administration of Orca-Q/OrcaGraft
Title
Acute GVHD through Day +100
Description
Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria
Time Frame
100 days after administration of Orca-Q/OrcaGraft
Title
Steroid-refractory acute GVHD through Day +100
Description
Steroid-refractory acute GVHD will be defined as per the EBMT-NIH-CIBMTR Task Force position statement
Time Frame
100 days after administration of Orca-Q/OrcaGraft
Title
Chronic GVHD through Day +365
Description
Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria
Time Frame
365 days after administration of Orca-Q/OrcaGraft
Title
Post-Transplant Lymphoproliferative Disorder (PTLD) through Day +365
Description
PTLD is defined as a biopsy consistent with the 2017 World Health Organization (WHO) classification of PTLD
Time Frame
365 days after administration of Orca-Q/OrcaGraft
Title
Incidence of non-relapse mortality (NRM) through Day +365
Description
NRM is defined as death without evidence of disease recurrence
Time Frame
365 days after administration of Orca-Q/OrcaGraft
Title
Incidence of disease relapse through Day +365
Description
Recurrence of primary disease for transplant
Time Frame
365 days after administration of Orca-Q/OrcaGraft
Title
GVHD-free and relapse-free survival (GRFS) through Day +365
Description
Survival free from GVHD and relapse
Time Frame
365 days after administration of Orca-Q/OrcaGraft
Title
Disease-free survival (DFS) through Day +365
Description
Disease-free survival is the time from date of transplant to death or relapse, whichever comes first.
Time Frame
365 days after administration of Orca-Q/OrcaGraft
Title
Overall survival through Day +365
Description
OS is defined as the time from the date of transplant to the date of death from any cause or, for surviving patients, to the date of last follow-up.
Time Frame
365 days after administration of Orca-Q/OrcaGraft

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: Age ≥ 18 and ≤ 65 years at the time of enrollment Diagnosed acute myeloid, lymphoid or mixed phenotype leukemia, or high or very high risk myelodysplasic syndrome (MDS) or Myelofibrosis Planned to undergo myeloablative allogeneic hematopoietic stem cell transplant (HCT) Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical 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 < 1.5 times upper limit of normal (ULN) (< 3 times if attributed to Gilbert's syndrome) and ALT/AST < 3 times ULN 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) Positive anti-donor HLA antibodies against a mismatched allele in the selected donor Karnofsky performance score < 70% (Appendix 12.7) Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) > 4 (Appendix 12.8) 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, HTLV-1 or -2 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 History of idiopathic or secondary myelofibrosis 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
1-530-414-9743
Email
info@orcabiosystems.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James S McClellan, MD, PhD
Organizational Affiliation
Orca Biosystems, Inc.
Official's Role
Study Director
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, MD
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
Mehrdad Abedi, MD
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
Robert Lowsky, MD
Facility Name
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
Facility Name
The University of Kansas Hospital
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph McGuirk, MD
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ayman Saad, MD
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samer Srour, MD
Facility Name
Froedtert Memorial Lutheran Hospital
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Withdrawn

12. IPD Sharing Statement

Learn more about this trial

A Phase 1 Study of Engineered Donor Grafts (Orca-Q) in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

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