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

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ClinicalTrials.gov Identifier: NCT03802695
Recruitment Status : Recruiting
First Posted : January 14, 2019
Last Update Posted : November 1, 2021
Sponsor:
Information provided by (Responsible Party):
Orca Biosystems, Inc.

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndromes Acute Leukemia Biological: OrcaGraft (Orca-Q) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 113 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Dose Escalation and Expansion Study of Engineered Donor Grafts Derived From Mobilized Peripheral Blood (OrcaGraft/Orca-Q), With Single Agent Graft Versus-host Disease Prophylaxis, in Recipients Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies
Actual Study Start Date : April 8, 2019
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : July 1, 2022


Arm Intervention/treatment
Experimental: Arm A
Recipients with HLA-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor; with single-agent GVHD prophylaxis given
Biological: OrcaGraft (Orca-Q)
engineered donor allograft

Experimental: Arm B
Recipients with haploidentical-related donors; with single-agent GVHD prophylaxis given
Biological: OrcaGraft (Orca-Q)
engineered donor allograft

Experimental: Arm C
Recipients with an HLA-identical related or unrelated donor; no GVHD prophylaxis given
Biological: OrcaGraft (Orca-Q)
engineered donor allograft




Primary Outcome Measures :
  1. Number of Dose Limiting Toxicities [ Time Frame: 28 Days after administration of Orca-Q/OrcaGraft ]
    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

  2. Primary Graft failure through Day +28 (dose expansion) [ Time Frame: 28 Days after administration of Orca-Q/OrcaGraft ]
    Primary graft failure in the dose expansion phase, defined as being alive without recovery of neutrophils during the evaluation period


Secondary Outcome Measures :
  1. Neutrophil Engraftment through Day +28 [ Time Frame: 28 days after administration of Orca-Q/OrcaGraft ]
    Neutrophil engraftment defined as an absolute neutrophil count of >/=500/mm3 for 3 consecutive days

  2. Platelet engraftment through Day +50 [ Time Frame: 50 days after administration of Orca-Q/OrcaGraft ]
    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

  3. Secondary graft failure through Day +100 [ Time Frame: 100 days after administration of Orca-Q/OrcaGraft ]
    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

  4. Treatment-emergent adverse events (TEAEs) through the safety reporting period [ Time Frame: 100 days after administration of Orca-Q/OrcaGraft ]
    TEAEs categorized by System Organ Lass and graded according to the CTCAE v5.0

  5. Acute GVHD through Day +100 [ Time Frame: 100 days after administration of Orca-Q/OrcaGraft ]
    Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria

  6. Steroid-refractory acute GVHD through Day +100 [ Time Frame: 100 days after administration of Orca-Q/OrcaGraft ]
    Steroid-refractory acute GVHD will be defined as per the EBMT-NIH-CIBMTR Task Force position statement

  7. Chronic GVHD through Day +365 [ Time Frame: 365 days after administration of Orca-Q/OrcaGraft ]
    Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria

  8. Post-Transplant Lymphoproliferative Disorder (PTLD) through Day +365 [ Time Frame: 365 days after administration of Orca-Q/OrcaGraft ]
    PTLD is defined as a biopsy consistent with the 2017 World Health Organization (WHO) classification of PTLD

  9. Incidence of non-relapse mortality (NRM) through Day +365 [ Time Frame: 365 days after administration of Orca-Q/OrcaGraft ]
    NRM is defined as death without evidence of disease recurrence

  10. Incidence of disease relapse through Day +365 [ Time Frame: 365 days after administration of Orca-Q/OrcaGraft ]
    Recurrence of primary disease for transplant

  11. GVHD-free and relapse-free survival (GRFS) through Day +365 [ Time Frame: 365 days after administration of Orca-Q/OrcaGraft ]
    Survival free from GVHD and relapse

  12. Disease-free survival (DFS) through Day +365 [ Time Frame: 365 days after administration of Orca-Q/OrcaGraft ]
    Disease-free survival is the time from date of transplant to death or relapse, whichever comes first.

  13. Overall survival through Day +365 [ Time Frame: 365 days after administration of Orca-Q/OrcaGraft ]
    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.



Information from the National Library of Medicine

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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:

  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03802695


Contacts
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Contact: James S McClellan, MD, PhD 1-530-414-9743 info@orcabiosystems.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Amandeep Salhotra, MD         
UC Davis Recruiting
Sacramento, California, United States, 95817
Contact: Mehrdad Abedi, MD         
Stanford Health Care Recruiting
Stanford, California, United States, 94305
Contact: Robert Lowsky, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Edmund Waller, MD         
United States, Kansas
The University of Kansas Hospital Recruiting
Kansas City, Kansas, United States, 66160
Contact: Joseph McGuirk, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Ayman Saad, MD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77054
Contact: Samer Srour, MD         
United States, Wisconsin
Froedtert Memorial Lutheran Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Sameem Abedin, MD, PhD         
Sponsors and Collaborators
Orca Biosystems, Inc.
Investigators
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Study Director: James S McClellan, MD, PhD Orca Biosystems, Inc.
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Responsible Party: Orca Biosystems, Inc.
ClinicalTrials.gov Identifier: NCT03802695    
Other Study ID Numbers: OGFT001-001
First Posted: January 14, 2019    Key Record Dates
Last Update Posted: November 1, 2021
Last Verified: October 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Neoplasms
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site