RecruitingPhase 1NCT03802695

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

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


Sponsor

Orca Biosystems, Inc.

Enrollment

300 participants

Start Date

Apr 8, 2019

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 12 YearsMax Age: 78 Years

Inclusion Criteria11

  • 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 Criteria13

  • 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

Interventions

BIOLOGICALOrcaGraft (Orca-Q)

engineered donor allograft


Locations(9)

City of Hope

Duarte, California, United States

UC Davis

Sacramento, California, United States

Stanford Health Care

Stanford, California, United States

Moffitt Cancer Center

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

The University of Kansas Hospital

Kansas City, Kansas, United States

Ohio State University

Columbus, Ohio, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

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NCT03802695


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