Clinical trial NCT03802695: A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
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 Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndromes
Mixed Phenotype Acute Leukemia
Myelofibrosis
Chronic Myeloid Leukemia
Lead sponsor: Orca Biosystems, Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-14
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, and efficacy of engineered donor grafts ("OrcaGraft"/"Orca-Q") in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies.


Eligibility criteria: Key Inclusion Criteria:

1. Age ≥ 18 and ≤ 65 years at the time of enrollment
2. Diagnosed acute myeloid, lymphoid or mixed phenotype leukemia, or high or very high risk myelodysplasic syndrome (MDS), myelofibrosis, or chronic myeloid leukemia
3. Planned to undergo myeloablative allogeneic hematopoietic stem cell transplant (HCT)
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
6. Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
7. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
8. Total bilirubin \< 1.5 times upper limit of normal (ULN) (\< 3 times if attributed to Gilbert's syndrome) and ALT/AST \< 3 times ULN

Key Exclusion Criteria:

1. Prior allogeneic HCT
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. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor
5. Karnofsky performance score \< 70% (Appendix 12.7)
6. Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) \> 4 (Appendix 12.8)
7. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
8. Seropositive for HIV-1 or -2, HTLV-1 or -2
9. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
10. Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
11. History of idiopathic or secondary myelofibrosis
12. Women who are pregnant or breastfeeding

Primary outcomes:
measure: Number of Dose Limiting Toxicities
timeFrame: 28 Days after administration of Orca-Q/OrcaGraft
measure: Primary Graft failure through Day +28 (dose expansion)
timeFrame: 28 Days after administration of Orca-Q/OrcaGraft
Secondary outcomes:
measure: Neutrophil Engraftment through Day +28
timeFrame: 28 days after administration of Orca-Q/OrcaGraft
measure: Platelet engraftment through Day +50
timeFrame: 50 days after administration of Orca-Q/OrcaGraft
measure: Secondary graft failure through Day +100
timeFrame: 100 days after administration of Orca-Q/OrcaGraft
measure: Treatment-emergent adverse events (TEAEs) through the safety reporting period
timeFrame: 100 days after administration of Orca-Q/OrcaGraft
measure: Acute GVHD through Day +100
timeFrame: 100 days after administration of Orca-Q/OrcaGraft
measure: Steroid-refractory acute GVHD through Day +100
timeFrame: 100 days after administration of Orca-Q/OrcaGraft
measure: Chronic GVHD through Day +365
timeFrame: 365 days after administration of Orca-Q/OrcaGraft
measure: Post-Transplant Lymphoproliferative Disorder (PTLD) through Day +365
timeFrame: 365 days after administration of Orca-Q/OrcaGraft
measure: Incidence of non-relapse mortality (NRM) through Day +365
timeFrame: 365 days after administration of Orca-Q/OrcaGraft
measure: Incidence of disease relapse through Day +365
timeFrame: 365 days after administration of Orca-Q/OrcaGraft
measure: GVHD-free and relapse-free survival (GRFS) through Day +365
timeFrame: 365 days after administration of Orca-Q/OrcaGraft
measure: Disease-free survival (DFS) through Day +365
timeFrame: 365 days after administration of Orca-Q/OrcaGraft
measure: Overall survival through Day +365
timeFrame: 365 days after administration of Orca-Q/OrcaGraft
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital
state: Wisconsin
Study officials:
affiliation: Orca Biosystems, Inc.
name: James S McClellan, MD, PhD
role: STUDY_DIRECTOR
References: