Description:
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).
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
Interventions
Drug | Synonyms | Arms |
---|
Atezolizumab | Tecentriq | Atezolizumab + Hu5F9-G4 |
Hu5F9-G4 | | Atezolizumab + Hu5F9-G4 |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Atezolizumab + Hu5F9-G4 | Experimental | An 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. | |
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.
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 37 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 37M) |
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 37M);TDV(up to C16D21)(UTA 37M) |
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 37 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 37 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 37 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 37 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 37 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 37 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 37 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 37 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 37 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
December 14, 2020