Clinical Trial 23253

• Overview

  Study 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

  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.

  Objective:

  Primary: To assess the safety and tolerability of Orca-Q (formerly OrcaGraft) in adult participants undergoing myeloablative allogeneic hematopoietic cell transplantation (MA-alloHCT) or allogeneic hematopoietic cell transplantation using non-myeloablative/reduced-intensity conditioning (NMA/RIC-alloHCT). To identify the maximum tolerated dose (MTD) and to explore a recommended Phase 2 dose (RP2D) of the memory T-cell component of Orca-Q in adults undergoing MA alloHCT. Secondary: To explore the safety, tolerability and efficacy of Orca-Q in adult participants undergoing MA-alloHCT. To explore differences in the safety, tolerability, and efficacy of Orca-Q in adults undergoing matched related or unrelated, mismatched unrelated, or haploidentical-related MA-alloHCT or NMA/RIC-alloHCT.

• Treatments

  Therapies:

  Bone Marrow Transplant; Cell Therapy

  Medications:

  Orca-Q ()

• Inclusion Criteria

  Key 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 > Participants enrolling on NMA/RIC-alloHCT arms must be deemed unfit for a myeloablative alloHCT per assessment of the principal investigator (PI)

• Exclusion Criteria

  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) > 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

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