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

Orca Bio

Status and phase: Enrolling; Phase 1

Conditions: Mixed Phenotype Acute 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 allogeneic hematopoietic cell transplant (alloHCT) transplantation for hematologic malignancies.

Enrollment: 300 estimated patients

Sex: All

Ages: 12 to 78 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Age at the time of enrollment:

   1. For MAC with fully matched donor (Arm A with 8/8 donor and Arm C) and NMA/RIC: Age ≥ 12 and ≤ 78 years
   2. For MAC with mismatched donors (Arm A with 7/8 donor and Arm B): Age ≥ 12 and ≤ 65 years

2. 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)

3. Indicated for allogeneic hematopoietic stem cell transplant (alloHCT)

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 (MAC with tacrolimus) or > 30 mL/minute (NMA/RIC or MAC without tacrolimus)

6. Cardiac parameters: Cardiac ejection fraction ≥ 45 percent (MAC) or ≥ 40 percent (NMA/RIC)

7. Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50 percent for MAC or ≥ 40 percent for NMA/RIC

8. 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)

9. 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:

1. Prior alloHCT
2. 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
3. Planned donor lymphocyte infusion (DLI)
4. Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy) or alemtuzumab
5. Positive anti-donor HLA antibodies against a mismatched allele in the selected donor
6. Low performance score: For MAC: Karnofsky Performance Score (KPS) < 70 percent, For NMA/RIC: <60 percent
7. High HCT-specific Comorbidity Index (HCT-CI): For MAC > 4, For NMA/RIC >6
8. Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
9. 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)
10. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
11. 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
12. History of idiopathic or secondary myelofibrosis
13. 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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300 participants in 6 patient groups

Arm A

Experimental group

Description:

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

Treatment:

Biological: OrcaGraft (Orca-Q)

Arm B

Experimental group

Description:

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

Treatment:

Biological: OrcaGraft (Orca-Q)

Arm C

Experimental group

Description:

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

Treatment:

Biological: OrcaGraft (Orca-Q)

Arm D

Experimental group

Description:

Recipients with an HLA-identical related or unrelated donor undergoing non-myeloablative (NMA)/reduced intensity conditioning (RIC); with dual agent GVHD prophylaxis given

Treatment:

Biological: OrcaGraft (Orca-Q)

Arm E

Experimental group

Description:

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

Treatment:

Biological: OrcaGraft (Orca-Q)

Arm F

Experimental group

Description:

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

Treatment:

Biological: OrcaGraft (Orca-Q)