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

Orca Bio

Status and phase: Enrolling; Phase 1

Conditions: Myelofibrosis; Mixed Phenotype Acute Leukemia; Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Acute Myeloid Leukemia

Treatments: Biological: OrcaGraft (Orca-Q)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03802695

OGFT001-001

Details and patient eligibility

About

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.

Enrollment: 186 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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186 participants in 3 patient groups

Arm A

Experimental group

Description:

Recipients with HLA-identical or 1-allele mismatched (7/8 alleles) related or unrelated donor; with single-agent GVHD prophylaxis given

Treatment:

Biological: OrcaGraft (Orca-Q)

Arm B

Experimental group

Description:

Recipients with haploidentical-related donors; with single-agent GVHD prophylaxis given

Treatment:

Biological: OrcaGraft (Orca-Q)

Arm C

Experimental group

Description:

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

Treatment:

Biological: OrcaGraft (Orca-Q)