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

A Phase 1 Dose Escalation and Expansion Study of Orca-Q, an Engineered Donor Graft Derived From Mobilized Peripheral Blood, in Recipients Undergoing Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Acute Lymphoblastic Leukemia; Mixed Phenotype Acute Leukemia
• Intervention / Treatment: Biological: OrcaGraft (Orca-Q)

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tamara Zharkevich, MD, PhD; Phone Number: 650-246-9601; Email: info@orcabiosystems.com
• Study Contact Backup: Name: James S McClellan, MD PhD; Phone Number: 650-246-9601; Email: info@orcabiosystems.com

Study Locations

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      • Withdrawn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      • Withdrawn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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm C; Recipients with an HLA-identical related or unrelated donor undergoing MAC; no GVHD prophylaxis given	Biological: OrcaGraft (Orca-Q); engineered donor allograft
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); engineered donor allograft
Experimental: Arm F; Recipients with haploidentical-related donors undergoing NMA/RIC; with dual-agent GVHD prophylaxis given	Biological: OrcaGraft (Orca-Q); engineered donor allograft
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); engineered donor allograft
Experimental: Arm B; Recipients with haploidentical-related donors undergoing MAC; with single- or dual-agent GVHD prophylaxis given	Biological: OrcaGraft (Orca-Q); engineered donor allograft
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); engineered donor allograft

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	28 Days after administration of Orca-Q/OrcaGraft
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	28 Days after administration of Orca-Q/OrcaGraft

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil Engraftment through Day +28	Neutrophil engraftment defined as an absolute neutrophil count of >/=500/mm3 for 3 consecutive days	28 days after administration of Orca-Q/OrcaGraft
Acute GVHD through Day +100	Acute GVHD will be staged and graded per Mount Sinai Acute GvHD International Consortium (MAGIC) Standardization criteria	100 days after administration of Orca-Q/OrcaGraft
Chronic GVHD through Day +365	Chronic GVHD will be diagnosed per 2014 International NIH Chronic GVHD Diagnosis and Staging Consensus Working Group criteria	365 days after administration of Orca-Q/OrcaGraft
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	50 days after administration of Orca-Q/OrcaGraft
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	100 days after administration of Orca-Q/OrcaGraft
Incidence of Non-relapse Mortality (NRM) through Day +365	NRM is defined as death without evidence of disease recurrence	365 days after administration of Orca-Q/OrcaGraft
Incidence of Disease Relapse through Day +365	Recurrence of primary disease for transplant	365 days after administration of Orca-Q/OrcaGraft
GVHD-free and Relapse-free Survival (GRFS) through Day +365	Survival free from GVHD and relapse	365 days after administration of Orca-Q/OrcaGraft
Disease-free Survival (DFS) through Day +365	DFS is the time from date of transplant to death or relapse, whichever comes first.	365 days after administration of Orca-Q/OrcaGraft
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.	365 days after administration of Orca-Q/OrcaGraft

Collaborators and Investigators

• Sponsor: Orca Biosystems, Inc.
• Investigators: Study Director: James S McClellan, MD, PhD, Orca Biosystems, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2019
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 10, 2019
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (Actual): January 14, 2019

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Biphenotypic, Acute
• Other Study ID Numbers: OGFT001-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No