Acute Myeloid LeukemiaPhase 1NCT03802695
A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
A Phase 1 study testing OrcaGraft (Orca-Q) in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Orca Biosystems, Inc. at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 78 years
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Mixed Phenotype Acute Leukemia
- What is being tested?
- OrcaGraft (Orca-Q)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 12 sitesUnited States
- Study dates
- 8 Apr 2019to Dec 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 78 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
United States12 sites, 9 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30322
Edmund Waller, MD
- Active, not recruiting
Ohio State University
Columbus, Ohio, 43210
- Recruiting
City of Hope
Duarte, California, 91010
Amandeep Salhotra, MD
- Recruiting
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Siddhartha Reddy, MD
- Recruiting
University of Texas MD Anderson Cancer Center
Houston, Texas, 77054
Samer Srour, MD
- Withdrawn
The University of Kansas Hospital
Kansas City, Kansas, 66160
- Withdrawn
Froedtert Memorial Lutheran Hospital
Milwaukee, Wisconsin, 53226
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Roni Tamari, MD
- Recruiting
UC Davis
Sacramento, California, 95817
Mehrdad Abedi, MD
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Boglarka Gyurkocza, MD
- Recruiting
Stanford Health Care
Stanford, California, 94305
Robert Lowsky, MD
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Rawan Faramand, MD
About this study
Official title: 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.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Mixed Phenotype Acute Leukemia, Acute Lymphoblastic Leukemia
- Being tested
- OrcaGraft (Orca-Q)
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OrcaGraft (Orca-Q)Biological
engineered donor allograft
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: OrcaGraft (Orca-Q) |
| Arm B | Experimental | Recipients with haploidentical-related donors undergoing MAC; with single- or dual-agent GVHD prophylaxis given Receives: Biological: OrcaGraft (Orca-Q) |
| Arm C | Experimental | Recipients with an HLA-identical related or unrelated donor undergoing MAC; no GVHD prophylaxis given Receives: 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 Receives: 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 Receives: Biological: OrcaGraft (Orca-Q) |
| Arm F | Experimental | Recipients with haploidentical-related donors undergoing NMA/RIC; with dual-agent GVHD prophylaxis given Receives: Biological: OrcaGraft (Orca-Q) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 28 Days after administration of Orca-Q/OrcaGraft
Secondary outcomes (10)
Neutrophil Engraftment through Day +28
Neutrophil engraftment defined as an absolute neutrophil count of >/=500/mm3 for 3 consecutive days
Measured: 28 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
Measured: 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
Measured: 100 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
Measured: 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
Measured: 365 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
Measured: 365 days after administration of Orca-Q/OrcaGraft
Incidence of Disease Relapse through Day +365
Recurrence of primary disease for transplant
Measured: 365 days after administration of Orca-Q/OrcaGraft
GVHD-free and Relapse-free Survival (GRFS) through Day +365
Survival free from GVHD and relapse
Measured: 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.
Measured: 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.
Measured: 365 days after administration of Orca-Q/OrcaGraft
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2019
- Study start8 Apr 2019
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Orca Biosystems, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James S McClellan, MD, PhD, Study director, Orca Biosystems, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03802695
- Sponsor's protocol ID
- OGFT001-001
- Status last verified
- Sep 2026
- First submitted
- 10 Jan 2019
- Last updated
- 29 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
O'Neal J, Mavers M, Jayasinghe RG, DiPersio JF. Traversing the bench to bedside journey for iNKT cell therapies. Front Immunol. 2024 Aug 7;15:1436968. doi: 10.3389/fimmu.2024.1436968. eCollection 2024.
PubMed 39170618