A Study Evaluating the Safety and Pharmacokinetics of Atezolizumab Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Atezolizumab; Hu5F9-G4
Intervention description: Atezolizumab will be administered to participants by IV infusion at a fixed dose starting on Day 22 of Cycle 1. In subsequent cycles (Cycles 2 and beyond), IV atezolizumab will be given every 2 weeks (Q2W) on Days 8 and 22 of each 28-day cycle.; Two priming doses of 1 mg/kg of Hu5F9-G4 will be administered to participants by continuous IV infusion on Days 1 and 4 of Cycle 1, followed by loading doses of 15 mg/kg IV on Day 8 and 30 mg/kg IV on Day 11. Starting on Day 15 of Cycle 1, Hu5F9-G4 maintenance will be given by IV infusion at a dose of 30 mg/kg once a week (QW) of each 28-day cycle. Dosing for de-escalation, if needed: Hu5F9-G4 will be given as two priming doses of 1 mg/kg IV on Days 1 and 4, followed by loading doses of 10 mg/kg IV on Day 8 and 15 mg/kg on Day 11. Starting on Day 15, maintenance treatment with Hu5F9-G4 will be given by IV infusion at a dose of 15 mg/kg once a week (QW).
Intervention MeSH terms: Atezolizumab; Magrolimab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This Phase Ib study is designed to evaluate the safety and pharmacokinetics of atezolizumab
      when given in combination with Hu5F9-G4 to patients with relapsed or refractory (R/R) acute
      myeloid leukemia (AML).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Life expectancy of at least 12 weeks

          -  Eastern Cooperative Oncology Group Performance Status 0-2

          -  Documented and confirmed R/R AML per WHO classification, except acute promyelocytic
             leukemia, and lack of response to all therapies of known benefit

          -  Adequate end-organ function

          -  Negative HIV test at screening

          -  Negative hepatitis B surface antigen (HBsAg) test at screening

          -  Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total
             HBcAb test followed by quantitative hepatitis B virus (HBV) DNA <500 IU/mL at
             screening

          -  Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
             test followed by a negative HCV RNA test at screening

          -  Willingness and ability to provide pretreatment bone marrow aspirate and biopsy and
             agreement to provide subsequent bone marrow aspirates and biopsies during study
             treatment

          -  For women of childbearing potential: agreement to remain abstinent or use
             contraceptive methods, and agreement to refrain from donating eggs

          -  For men: agreement to remain abstinent or use contraceptive measures and agreement to
             refrain from donating sperm

          -  For women who are not postmenopausal or surgically sterile: requirement for a negative
             serum pregnancy test result within 14 days prior to initiation of study treatment

        Exclusion Criteria:

          -  Previous allogeneic hematopoietic stem cell transplant within 6 months prior to
             enrollment, active graft versus host disease, or requiring transplant-related
             immunosuppression

          -  Prior solid organ transplant

          -  Evidence of active central nervous system (CNS) involvement by leukemia

          -  Pregnancy or lactation or intention to become pregnant during the study or within 5
             months after the final dose of atezolizumab and/or Hu5F9-G4, whichever is longer

          -  History of idiopathic pulmonary fibrosis, organizing pneumonitis, drug-induced
             pneumonitis, or idiopathic pneumonitis

          -  History of autoimmune disease. Patients with a history of autoimmune-related
             hypothyroidism who are on a stable dose of thyroid replacement may be eligible for
             this study. Patients with controlled Type 1 diabetes mellitus who are on a stable
             insulin regimen may be eligible for this study. Patients with eczema, psoriasis,
             lichen simplex chronicus, or vitiligo with dermatologic manifestations only are
             eligible for the study provided all of the following conditions are met: (1) Rash must
             cover <10% of body surface area, (2) Disease is well controlled at baseline and
             requires only low-potency topical corticosteroids, (3) No occurrence of acute
             exacerbations of the underlying condition that require psoralen plus ultraviolet A
             radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or
             high-potency or oral corticosteroids within the previous 12 months.

          -  Treatment with investigational therapy within 14 days prior to initiation of study
             drug

          -  Any approved AML-related therapy within 14 days prior to enrollment. Granulocyte
             colony-stimulating factor to treat neutropenic fever and/or infection is permitted.
             Hydroxyurea may be used throughout the trial to control peripheral blood blast counts
             in response to the first dose of study treatment and during the first 4 weeks of study
             treatment.