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 Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

Overview

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.

Interventions

• Biological OrcaGraft (Orca-Q)
  engineered donor allograft

Primary outcome measures

• Dose Limiting Toxicities through Day +28 (dose escalation) [Time frame: 28 Days after administration of Orca-Q/OrcaGraft]
• Primary Graft failure through Day +28 (dose expansion) [Time frame: 28 Days after administration of Orca-Q/OrcaGraft]

Secondary outcome measures (10)

• Neutrophil Engraftment through Day +28 [Time frame: 28 days after administration of Orca-Q/OrcaGraft]
• Platelet Engraftment through Day +50 [Time frame: 50 days after administration of Orca-Q/OrcaGraft]
• Secondary Graft Failure through Day +100 [Time frame: 100 days after administration of Orca-Q/OrcaGraft]
• Acute GVHD through Day +100 [Time frame: 100 days after administration of Orca-Q/OrcaGraft]
• Chronic GVHD through Day +365 [Time frame: 365 days after administration of Orca-Q/OrcaGraft]
• Incidence of Non-relapse Mortality (NRM) through Day +365 [Time frame: 365 days after administration of Orca-Q/OrcaGraft]
• Incidence of Disease Relapse through Day +365 [Time frame: 365 days after administration of Orca-Q/OrcaGraft]
• GVHD-free and Relapse-free Survival (GRFS) through Day +365 [Time frame: 365 days after administration of Orca-Q/OrcaGraft]
• Disease-free Survival (DFS) through Day +365 [Time frame: 365 days after administration of Orca-Q/OrcaGraft]
• Overall Survival through Day +365 [Time frame: 365 days after administration of Orca-Q/OrcaGraft]

Eligibility criteria

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)

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 12 centers

• City of Hope — Duarte
• UC Davis — Sacramento
• Stanford Health Care — Stanford
• Moffitt Cancer Center — Tampa
• Emory University — Atlanta
• The University of Kansas Hospital — Kansas City
• John Theurer Cancer Center at Hackensack University Medical Center — Hackensack
• Memorial Sloan Kettering Cancer Center — New York
• … and 4 more centers

Identifiers

NCT: NCT03802695 · OGFT001-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗