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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

NCT03922477

Description:

This Phase Ib study is designed to evaluate the safety and pharmacokinetics of atezolizumab when given in combination with Hu5F9-F4 to patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Phase Ib, Open-Label Study Evaluating the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: GO40828
  • NCT ID: NCT03922477

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
AtezolizumabTecentriqAtezolizumab + Hu5F9-F4
Hu5F9-G4Atezolizumab + Hu5F9-F4

Purpose

This Phase Ib study is designed to evaluate the safety and pharmacokinetics of atezolizumab when given in combination with Hu5F9-F4 to patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab + Hu5F9-F4ExperimentalAn initial safety evaluation will be performed in participants with relapsed AML. If atezolizumab in combination with Hu5F9-G4 is initially safe and tolerable in participants an additional cohort with R/R AML will be evaluated to further test the safety and anti-tumor activity. If dose-limiting toxicities (DLT) are observed in >=33% of participants in this initial cohort, a dose de-escalation cohort will be enrolled. If less than 33% of enrolled and dosed participants in any given cohort experience a DLT, an expansion cohort of 15 participants will be enrolled at the highest tolerated dose for this combination. If a dose de-escalation cohort is needed, an expansion cohort will be enrolled at the lower tolerated dose for this combination.
  • Atezolizumab
  • Hu5F9-G4

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 using the World Health Organization's classification,
             except acute promyelocytic leukemia

          -  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 28 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 to control peripheral blood blast counts in response to the
             first dose of study treatment and during the first 4 weeks of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events
Time Frame:Up to approximately 32 months after first participant enrolled
Safety Issue:
Description:The CR rate will be assessed as the percentage of participants who achieve a CR, complete remission with incomplete platelet recovery (CRp), complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh) (as defined by the IWG 2003 and ELN 2010 criteria) after up to six cycles of combination therapy.

Secondary Outcome Measures

Measure:Serum Concentrations of Atezolizumab
Time Frame:C1 D22 PTFI of Hu5F9-G4 and atezolizumab, and 30 minutes after atezolizumab infusion; C2 D8 PTFI; C2 D22 PTFI; C3 D22 PTFI; C4 D22 PTFI; C8 D22 PTFI; C12 D22 PTFI; C16 D22 PTFI; TDV (up to C16 D21);120 days after final dose of atezolizumab (UTA 32M)
Safety Issue:
Description:C=cycle (cycle=28 days) ; D=day; PTFI=prior to first infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=month
Measure:Serum Concentrations of Hu5F9-G4
Time Frame:C1D1 PTFI&1H AEOI; C1D8 PTFI,&1H AEOI; C1D11 PTFI,&1H AEOI; C1D22 1H AEOI; C2D1 PTFI,&1H AEOI; C2D8 PTFI; C3D1 PTFI,&1H AEOI; C5D1 PTFI; C7D1 PTFI, C9D1 PTFI; C11D1 PTFI; C13D1 PTFI; C15D1 PTFI; C17D1&D1 E 2C T PTFI(UTA 32M);TDV(up to C16D21)(UTA 32M)
Safety Issue:
Description:C=cycle (cycle=28 days); D=Day; PTFI=prior to first infusion; H=hour; AEOI=after end of infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=months; E=every; T=thereafter
Measure:Objective Response Rate
Time Frame:Up to approximately 32 months after first participant enrolled
Safety Issue:
Description:Defined as the percentage of patients with a partial remission (PR) or better (i.e., CR + CRp + CRi + CRh+ PR)
Measure:Event-Free Survival
Time Frame:Up to approximately 32 months after first participant enrolled
Safety Issue:
Description:Defined as the time from study entry to the date of induction treatment failure or relapse from CR, CRp, CRh, CRi, or death from any cause
Measure:Leukemia-Free Survival
Time Frame:Up to approximately 32 months after first participant enrolled
Safety Issue:
Description:Defined (only for patients achieving a CR, CRp, CRh, or CRi) as the time from the date of achievement of remission (CR, CRp, or CRi) until the date of relapse from CR, CRp, CRh, CRi, or death from any cause
Measure:Overall Survival
Time Frame:Up to approximately 32 months after first participant enrolled
Safety Issue:
Description:Defined as time from study entry to the date of death from any cause.
Measure:Progression-Free Survival
Time Frame:Up to approximately 32 months after first participant enrolled
Safety Issue:
Description:Defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.
Measure:Rate of Transfusion Independence
Time Frame:Up to approximately 32 months after first participant enrolled
Safety Issue:
Description:Defined as the percentage of patients who achieve transfusion independence (i.e., achieving any continuous 56-day window without requiring platelet or RBC transfusions) at any time during study treatment.
Measure:Duration of Transfusion Independence
Time Frame:Up to approximately 32 months after first participant enrolled
Safety Issue:
Description:Defined as the number of consecutive days of transfusion independence, measured from 1 day after the last transfusion to disease progression or subsequent transfusion.
Measure:Incidence of Anti-Drug Antibodies (ADAs) Against Atezolizumab During the Study Relative to the Prevalence of ADAs at Baseline
Time Frame:Baseline up to approximately 32 months
Safety Issue:
Description:
Measure:Incidence of ADAs Against Hu5F9-G4 During the Study Relative to the Prevalence of ADAs at Baseline
Time Frame:Baseline up to approximately 32 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

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