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

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Mixed Phenotype Acute Leukemia
• Interventions: Biological: OrcaGraft (Orca-Q)

• Registration Number: NCT03802695
• Lead Sponsor: Orca Biosystems, Inc.

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-10
• Study First Submitted QC: 2019-01-10
• Study First Posted: 2019-01-14
• Study Start: 2019-04-08
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-25
• Last Update Posted: 2025-09-02
• Primary Completion: 2027-12
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Age ≥ 12 and ≤ 78 years at the time of enrollment
2. Diagnosed acute myeloid, lymphoid or mixed phenotype leukemia, or high or very high risk myelodysplasic syndrome (MDS) either in complete remission (CR) or with ≤ 10 percent of blast cells in bone marrow (BM)
3. Planned to undergo 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. 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
12. History of idiopathic or secondary myelofibrosis
13. Women who are pregnant or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	OrcaGraft (Orca-Q)	Recipients with human leukocyte antigen (HLA)-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor undergoing myeloablative conditioning (MAC); with single-agent graft-versus-host disease (GVHD) prophylaxis given
Arm B	OrcaGraft (Orca-Q)	Recipients with haploidentical-related donors undergoing MAC; with single-agent GVHD prophylaxis given
Arm C	OrcaGraft (Orca-Q)	Recipients with an HLA-identical related or unrelated donor undergoing MAC; no GVHD prophylaxis given
Arm D	OrcaGraft (Orca-Q)	Recipients with an HLA-identical related or unrelated donor undergoing non-myeloablative (NMA)/reduced intensity conditioning (RIC); with dual agent GVHD prophylaxis
Arm E	OrcaGraft (Orca-Q)	Recipients with 1-allele mismatched (7/8 alleles) unrelated donor undergoing NMA/RIC; with dual-agent GVHD prophylaxis given
Arm F	OrcaGraft (Orca-Q)	Recipients with haploidentical-related donors undergoing NMA/RIC; with dual-agent GVHD prophylaxis given

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicities through Day +28 (dose escalation)	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
Primary Graft failure through Day +28 (dose expansion)	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

Name	Time	Method
Neutrophil Engraftment through Day +28	28 days after administration of Orca-Q/OrcaGraft	Neutrophil engraftment defined as an absolute neutrophil count of \>/=500/mm3 for 3 consecutive days
Platelet Engraftment through Day +50	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
Secondary Graft Failure through Day +100	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
Acute GVHD through Day +100	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
Chronic GVHD through Day +365	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
Incidence of Non-relapse Mortality (NRM) through Day +365	365 days after administration of Orca-Q/OrcaGraft	NRM is defined as death without evidence of disease recurrence
Incidence of Disease Relapse through Day +365	365 days after administration of Orca-Q/OrcaGraft	Recurrence of primary disease for transplant
GVHD-free and Relapse-free Survival (GRFS) through Day +365	365 days after administration of Orca-Q/OrcaGraft	Survival free from GVHD and relapse
Disease-free Survival (DFS) through Day +365	365 days after administration of Orca-Q/OrcaGraft	DFS is the time from date of transplant to death or relapse, whichever comes first.
Overall Survival through Day +365	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.

Trial Locations

Locations (8)

City of Hope; 🇺🇸 Duarte, California, United States

UC Davis; 🇺🇸 Sacramento, California, United States

Stanford Health Care; 🇺🇸 Stanford, California, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

The University of Kansas Hospital; 🇺🇸 Kansas City, Kansas, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Froedtert Memorial Lutheran Hospital; 🇺🇸 Milwaukee, Wisconsin, United States