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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Orca Biosystems, Inc.
- Enrollment
- 300
- Locations
- 20
- Primary Endpoint
- Primary Graft failure through Day +28 (dose expansion)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non-randomized
- Intervention Model
- Parallel assignment
- Primary Purpose
- Treatment
- Masking
- None (open label)
Eligibility Criteria
- Ages
- 12 Years to 78 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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)
- Key
Exclusion Criteria
- 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
Arms & Interventions
Arm B
Recipients with haploidentical-related donors undergoing MAC; with single- or dual-agent GVHD prophylaxis given
Intervention: OrcaGraft (Orca-Q) (Biological)
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
Intervention: OrcaGraft (Orca-Q) (Biological)
Arm E
Recipients with 1-allele mismatched (7/8 alleles) unrelated donor undergoing NMA/RIC; with dual-agent GVHD prophylaxis given
Intervention: OrcaGraft (Orca-Q) (Biological)
Arm F
Recipients with haploidentical-related donors undergoing NMA/RIC; with dual-agent GVHD prophylaxis given
Intervention: OrcaGraft (Orca-Q) (Biological)
Arm C
Recipients with an HLA-identical related or unrelated donor undergoing MAC; no GVHD prophylaxis given
Intervention: OrcaGraft (Orca-Q) (Biological)
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
Intervention: OrcaGraft (Orca-Q) (Biological)
Outcomes
Primary Outcomes
Primary Graft failure through Day +28 (dose expansion)
Time Frame: 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
Dose Limiting Toxicities through Day +28 (dose escalation)
Time Frame: 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
Primary Graft failure through Day +28 (dose expansion)
Time Frame: 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 Outcomes
- Neutrophil Engraftment through Day +28(28 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)
- 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)
- Incidence of Non-relapse Mortality (NRM) through Day +365(365 days after administration of Orca-Q/OrcaGraft)
- Incidence of Disease Relapse through Day +365(365 days after administration of Orca-Q/OrcaGraft)
- GVHD-free and Relapse-free Survival (GRFS) through Day +365(365 days after administration of Orca-Q/OrcaGraft)
- Disease-free Survival (DFS) through Day +365(365 days after administration of Orca-Q/OrcaGraft)
- Overall Survival through Day +365(365 days after administration of Orca-Q/OrcaGraft)
Investigators
Study Sites (20)
Identifiers
- NCT ID
- NCT03802695
- Other Study IDs
- OGFT001-001
Dates
- First Submitted
- (7 years ago)
- First Posted
- (7 years ago)
- Primary Completion
- (next year)
- Study Completion
- (next year)
- Last Verified
- (29 days ago)
- Last updated
- (yesterday)
Regulatory & Sharing
- FDA Regulated Drug
- Yes
- FDA Regulated Device
- No
- Has Results
- No