NCT03802695

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
300

participants targeted

Target at P75+ for phase_1

Timeline
19mo left

Started Apr 2019

Longer than P75 for phase_1

Geographic Reach
1 country

9 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress82%
Apr 2019Dec 2027

First Submitted

Initial submission to the registry

January 10, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 14, 2019

Completed
3 months until next milestone

Study Start

First participant enrolled

April 8, 2019

Completed
8.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

February 23, 2026

Status Verified

February 1, 2026

Enrollment Period

8.7 years

First QC Date

January 10, 2019

Last Update Submit

February 19, 2026

Conditions

Acute Myeloid LeukemiaMyelodysplastic SyndromesMixed Phenotype Acute LeukemiaAcute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

  • 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

  • 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

Secondary Outcomes (10)

  • Neutrophil Engraftment through Day +28

    28 days after administration of Orca-Q/OrcaGraft

  • Platelet Engraftment through Day +50

    50 days after administration of Orca-Q/OrcaGraft

  • Secondary Graft Failure through Day +100

    100 days after administration of Orca-Q/OrcaGraft

  • Acute GVHD through Day +100

    100 days after administration of Orca-Q/OrcaGraft

  • Chronic GVHD through Day +365

    365 days after administration of Orca-Q/OrcaGraft

  • +5 more secondary outcomes

Study Arms (6)

Arm A

EXPERIMENTAL

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)

Arm B

EXPERIMENTAL

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

Biological: OrcaGraft (Orca-Q)

Arm C

EXPERIMENTAL

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

Biological: OrcaGraft (Orca-Q)

Arm D

EXPERIMENTAL

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)

Arm E

EXPERIMENTAL

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

Biological: OrcaGraft (Orca-Q)

Arm F

EXPERIMENTAL

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

Biological: OrcaGraft (Orca-Q)

Interventions

OrcaGraft (Orca-Q)BIOLOGICAL

engineered donor allograft

Arm AArm BArm CArm DArm EArm F

Eligibility Criteria

Age12 Years - 78 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Age at the time of enrollment:
  • For MAC with fully matched donor (Arm A with 8/8 donor and Arm C) and NMA/RIC: Age ≥ 12 and ≤ 78 years
  • For MAC with mismatched donors (Arm A with 7/8 donor and Arm B): Age ≥ 12 and ≤ 65 years
  • 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)
  • Indicated for allogeneic hematopoietic stem cell transplant (alloHCT)
  • 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 (MAC with tacrolimus) or \> 30 mL/minute (NMA/RIC or MAC without tacrolimus)
  • Cardiac parameters: Cardiac ejection fraction ≥ 45 percent (MAC) or ≥ 40 percent (NMA/RIC)
  • Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50 percent for MAC or ≥ 40 percent for NMA/RIC
  • 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)
  • Participants enrolling on NMA/RIC-alloHCT arms must be deemed unfit for a myeloablative alloHCT per assessment of the principal investigator (PI)

You may not qualify if:

  • Prior alloHCT
  • 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
  • Planned donor lymphocyte infusion (DLI)
  • Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy) or alemtuzumab
  • Positive anti-donor HLA antibodies against a mismatched allele in the selected donor
  • Low performance score: For MAC: Karnofsky Performance Score (KPS) \< 70 percent, For NMA/RIC: \<60 percent
  • High HCT-specific Comorbidity Index (HCT-CI): For MAC \> 4, For NMA/RIC \>6
  • Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
  • 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)
  • 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. 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
  • History of idiopathic or secondary myelofibrosis
  • Women who are pregnant or breastfeeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

City of Hope

Duarte, California, 91010, United States

RECRUITING

UC Davis

Sacramento, California, 95817, United States

RECRUITING

Stanford Health Care

Stanford, California, 94305, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

ACTIVE NOT RECRUITING

The University of Kansas Hospital

Kansas City, Kansas, 66160, United States

WITHDRAWN

Ohio State University

Columbus, Ohio, 43210, United States

ACTIVE NOT RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77054, United States

RECRUITING

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

WITHDRAWN

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteMyelodysplastic SyndromesLeukemia, Biphenotypic, AcutePrecursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow DiseasesLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • James S McClellan, MD, PhD

    Orca Biosystems, Inc.

    STUDY DIRECTOR

Central Study Contacts

Tamara Zharkevich, MD, PhD

CONTACT

650-246-9601info@orcabiosystems.com

James S McClellan, MD PhD

CONTACT

650-246-9601info@orcabiosystems.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2019

First Posted

January 14, 2019

Study Start

April 8, 2019

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

February 23, 2026

Record last verified: 2026-02

Locations

US(9)