Back to resultsA Study Evaluating the Safety and Pharmacokinetics of Atezolizumab Administered in Combination With Hu5F9-G4 to Patients With Relapsed and/or Refractory Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Atezolizumab
Hu5F9-G4
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
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.
Sites / Locations
- UC Davis Comprehensive Cancer Center
- Yale
- Columbia University
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Atezolizumab + Hu5F9-G4
Arm Description
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With Adverse Events
Percentage of participants with at least one adverse event.
Complete Remission (CR)
The CR rate is 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.
Duration of Response (DOR)
DOR is defined as the time from the initial response (CR, CRp, CRi, CRh, or partial remission [PR]) to the time of disease progression or death, whichever occurs first
Secondary Outcome Measures
Serum Concentrations of Atezolizumab
C=cycle (cycle=28 days) ; D=day; PTFI=prior to first infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=month
Serum Concentrations of Hu5F9-G4
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
Objective Response Rate
Objective response rate is defined as the percentage of participants with a partial remission (PR) or better (i.e., CR + CRp + CRi + CRh+ PR).
Event-Free Survival
Event-free survival is 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.
Leukemia-Free Survival
Leukemia-free survival is defined (only for participants 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.
Overall Survival
Overall survival is defined as time from study entry to the date of death from any cause.
Progression-Free Survival
Progression-free survival (Investigator) is defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.
Rate of Transfusion Independence
Rate of transfusion independence is defined as the percentage of participants who achieve transfusion independence (i.e., achieving any continuous 56-day window without requiring platelet or RBC transfusions) at any time during study treatment.
Duration of Transfusion Independence
Duration of transfusion independence is defined as the number of consecutive days of transfusion independence, measured from 1 day after the last transfusion to disease progression or subsequent transfusion.
Incidence of Anti-Drug Antibodies (ADAs) Against Atezolizumab During the Study Relative to the Prevalence of ADAs at Baseline
Incidence of ADAs Against Hu5F9-G4 During the Study Relative to the Prevalence of ADAs at Baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03922477
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
The Sponsor decided to discontinue the development of atezolizumab in combination with magrolimab in the AML indication.
Study Start Date
October 8, 2019 (Actual)
Primary Completion Date
November 3, 2020 (Actual)
Study Completion Date
November 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Atezolizumab + Hu5F9-G4
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
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.
Intervention Type
Drug
Intervention Name(s)
Hu5F9-G4
Intervention Description
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).
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events
Description
Percentage of participants with at least one adverse event.
Time Frame
Up to approximately 13 months after first participant enrolled
Title
Complete Remission (CR)
Description
The CR rate is 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.
Time Frame
Up to approximately 3 months after first participant enrolled
Title
Duration of Response (DOR)
Description
DOR is defined as the time from the initial response (CR, CRp, CRi, CRh, or partial remission [PR]) to the time of disease progression or death, whichever occurs first
Time Frame
Up to approximately 3 months after first particpant enrolled
Secondary Outcome Measure Information:
Title
Serum Concentrations of Atezolizumab
Description
C=cycle (cycle=28 days) ; D=day; PTFI=prior to first infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=month
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)
Title
Serum Concentrations of Hu5F9-G4
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
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)
Title
Objective Response Rate
Description
Objective response rate is defined as the percentage of participants with a partial remission (PR) or better (i.e., CR + CRp + CRi + CRh+ PR).
Time Frame
Up to approximately 3 months after first participant enrolled
Title
Event-Free Survival
Description
Event-free survival is 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.
Time Frame
Up to approximately 3 months after first participant enrolled
Title
Leukemia-Free Survival
Description
Leukemia-free survival is defined (only for participants 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.
Time Frame
Up to approximately 3 months after first participant enrolled
Title
Overall Survival
Description
Overall survival is defined as time from study entry to the date of death from any cause.
Time Frame
Up to approximately 13 months after first participant enrolled
Title
Progression-Free Survival
Description
Progression-free survival (Investigator) is defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.
Time Frame
Up to approximately 3 months after first participant enrolled
Title
Rate of Transfusion Independence
Description
Rate of transfusion independence is defined as the percentage of participants who achieve transfusion independence (i.e., achieving any continuous 56-day window without requiring platelet or RBC transfusions) at any time during study treatment.
Time Frame
Up to approximately 3 months after first participant enrolled
Title
Duration of Transfusion Independence
Description
Duration of transfusion independence is defined as the number of consecutive days of transfusion independence, measured from 1 day after the last transfusion to disease progression or subsequent transfusion.
Time Frame
Up to approximately 3 months after first participant enrolled
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
UC Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Yale
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032-3725
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Learn more about this trial
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
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