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RecruitingNCT03802695Updated Sep 29, 2026

A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

A Phase 1 interventional study of OrcaGraft (Orca-Q) in Acute Myeloid Leukemia, Myelodysplastic Syndromes and Mixed Phenotype Acute Leukemia, sponsored by Orca Biosystems, Inc.. Recruiting at 12 sites in United States. Open to participants aged 12 Years to 78 Years. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by Orca Biosystems, Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
300
Allocation
Non-randomized
Ages
12 Years to 78 Years
Sex
All
01

Study summary

This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts ("OrcaGraft"/"Orca-Q") in participants undergoing allogeneic hematopoietic cell transplant (alloHCT) transplantation for hematologic malignancies.

02

Conditions studied

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Mixed Phenotype Acute Leukemia
  • Acute Lymphoblastic Leukemia
03

Who can participate

Ages eligible
12 Years to 78 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  1. Age at the time of enrollment:

    1. For MAC with fully matched donor (Arm A with 8/8 donor and Arm C) and NMA/RIC: Age ≥ 12 and ≤ 78 years
    2. For MAC with mismatched donors (Arm A with 7/8 donor and Arm B): Age ≥ 12 and ≤ 65 years
  2. Diagnosed acute myeloid, lymphoblastic or mixed phenotype leukemia, or high or very high risk myelodysplastic syndrome (MDS) either in complete remission (CR) or with ≤ 10 percent of blast cells in bone marrow (BM)
  3. Indicated for allogeneic hematopoietic stem cell transplant (alloHCT)
  4. Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical donor
  5. Estimated glomerular filtration rate (eGFR) > 50 mL/minute (MAC with tacrolimus) or > 30 mL/minute (NMA/RIC or MAC without tacrolimus)
  6. Cardiac parameters: Cardiac ejection fraction ≥ 45 percent (MAC) or ≥ 40 percent (NMA/RIC)
  7. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50 percent for MAC or ≥ 40 percent for NMA/RIC
  8. Liver function: Total bilirubin \< 1.5 times upper limit of normal (ULN) (MAC) or \< 3 times ULN (NMA/RIC); alanine transaminase (ALT)/aspartate transaminase (AST) \< 3 times ULN (MAC) or \< 5 times ULN (NMA/RIC)
  9. Participants enrolling on NMA/RIC-alloHCT arms must be deemed unfit for a myeloablative alloHCT per assessment of the principal investigator (PI)

Key Exclusion Criteria:

  1. Prior alloHCT
  2. Currently receiving corticosteroids or other immunosuppressive therapy except for approved disease-specific therapy for the patient's underlying hematologic malignancy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed
  3. Planned donor lymphocyte infusion (DLI)
  4. Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy) or alemtuzumab
  5. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor
  6. Low performance score: For MAC: Karnofsky Performance Score (KPS) \< 70 percent, For NMA/RIC: \<60 percent
  7. High HCT-specific Comorbidity Index (HCT-CI): For MAC > 4, For NMA/RIC >6
  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 human immunodeficiency virus (HIV)-1 or -2, human T-lymphotropic virus (HTLV)-1 or -2 or Hepatitis B surface antigen (HbsAg) or anti-Hepatitis C virus (HCV) antibody (Ab)
  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. Patients with concurrent indolent hematologic malignancies that do not require active treatment and are under active surveillance only (such as CLL, low-grade lymphomas, smoldering MM, MZL) may be included with the approval of Medical Monitor
  12. History of idiopathic or secondary myelofibrosis
  13. Women who are pregnant or breastfeeding
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
300 participants (estimated)

Study arms

  • Experimental
    Arm A

    Recipients with human leukocyte antigen (HLA)-identical related or unrelated or 1-allele mismatched (7/8 alleles) unrelated donor undergoing myeloablative conditioning (MAC); with single- or dual-agent graft-versus-host disease (GVHD) prophylaxis given

    Biological: OrcaGraft (Orca-Q)

  • Experimental
    Arm B

    Recipients with haploidentical-related donors undergoing MAC; with single- or dual-agent GVHD prophylaxis given

    Biological: OrcaGraft (Orca-Q)

  • Experimental
    Arm C

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

    Biological: OrcaGraft (Orca-Q)

  • Experimental
    Arm D

    Recipients with an HLA-identical related or unrelated donor undergoing non-myeloablative (NMA)/reduced intensity conditioning (RIC); with dual agent GVHD prophylaxis given

    Biological: OrcaGraft (Orca-Q)

  • Experimental
    Arm E

    Recipients with 1-allele mismatched (7/8 alleles) unrelated donor undergoing NMA/RIC; with dual-agent GVHD prophylaxis given

    Biological: OrcaGraft (Orca-Q)

  • Experimental
    Arm F

    Recipients with haploidentical-related donors undergoing NMA/RIC; with dual-agent GVHD prophylaxis given

    Biological: OrcaGraft (Orca-Q)

Interventions

  • BiologicalOrcaGraft (Orca-Q)

    engineered donor allograft

05

What researchers measure

Primary outcomes

  1. Dose Limiting Toxicities through Day +28 (dose escalation)

    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

    Time frame: 28 Days after administration of Orca-Q/OrcaGraft

  2. 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

    Time frame: 28 Days after administration of Orca-Q/OrcaGraft

Secondary outcomes

  1. Neutrophil Engraftment through Day +28

    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

  2. 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

    Time frame: 50 days after administration of Orca-Q/OrcaGraft

  3. 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

    Time frame: 100 days after administration of Orca-Q/OrcaGraft

  4. Acute GVHD through Day +100

    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

  5. Chronic GVHD through Day +365

    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

  6. Incidence of Non-relapse Mortality (NRM) through Day +365

    NRM is defined as death without evidence of disease recurrence

    Time frame: 365 days after administration of Orca-Q/OrcaGraft

  7. Incidence of Disease Relapse through Day +365

    Recurrence of primary disease for transplant

    Time frame: 365 days after administration of Orca-Q/OrcaGraft

  8. GVHD-free and Relapse-free Survival (GRFS) through Day +365

    Survival free from GVHD and relapse

    Time frame: 365 days after administration of Orca-Q/OrcaGraft

  9. Disease-free Survival (DFS) through Day +365

    DFS is the time from date of transplant to death or relapse, whichever comes first.

    Time frame: 365 days after administration of Orca-Q/OrcaGraft

  10. 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.

    Time frame: 365 days after administration of Orca-Q/OrcaGraft

06

Study locations

9 of 12 sites recruiting
  • City of Hope
    Duarte, California 91010, United States
    • Amandeep Salhotra, MD · Contact
    Recruiting
  • UC Davis
    Sacramento, California 95817, United States
    • Mehrdad Abedi, MD · Contact
    Recruiting
  • Stanford Health Care
    Stanford, California 94305, United States
    • Robert Lowsky, MD · Contact
    Recruiting
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
    • Rawan Faramand, MD · Contact
    Recruiting
  • Emory University
    Atlanta, Georgia 30322, United States
    • Edmund Waller, MD · Contact
    Recruiting
  • The University of Kansas Hospital
    Kansas City, Kansas 66160, United States
    Withdrawn
  • John Theurer Cancer Center at Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
    • Siddhartha Reddy, MD · Contact
    Recruiting
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
    • Roni Tamari, MD · Contact
    Recruiting
  • Ohio State University
    Columbus, Ohio 43210, United States
    Active, not recruiting
  • University of Texas MD Anderson Cancer Center
    Houston, Texas 77054, United States
    • Samer Srour, MD · Contact
    Recruiting
  • Fred Hutchinson Cancer Center
    Seattle, Washington 98109, United States
    • Boglarka Gyurkocza, MD · Contact
    Recruiting
  • Froedtert Memorial Lutheran Hospital
    Milwaukee, Wisconsin 53226, United States
    Withdrawn
07

Registry details

Key details

Study ID
NCT03802695
Lead sponsor
Orca Biosystems, Inc.
Responsible party
Sponsor
First posted
Jan 14, 2019
Start date
Apr 8, 2019
Primary completion
Dec 2027 (estimated)
Completion
Dec 2027 (estimated)
Last update
Sep 29, 2026

Study contacts

Tamara Zharkevich, MD, PhD
Contact
info@orcabiosystems.com
650-246-9601
James S McClellan, MD PhD
Contact
info@orcabiosystems.com
650-246-9601
James S McClellan, MD, PhD
study director · Orca Biosystems, Inc.

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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