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

December 3, 2021 updated by: Hoffmann-La Roche

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

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).

Study Overview

Status

Terminated

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Sacramento, California, United States, 95817
        • UC Davis Comprehensive Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale
    • New York
      • New York, New York, United States, 10032-3725
        • Columbia University
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Atezolizumab + Hu5F9-G4
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.
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.
Other Names:
  • Tecentriq
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Adverse Events
Time Frame: Up to approximately 13 months after first participant enrolled
Percentage of participants with at least one adverse event.
Up to approximately 13 months after first participant enrolled
Complete Remission (CR)
Time Frame: Up to approximately 3 months after first participant enrolled
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.
Up to approximately 3 months after first participant enrolled
Duration of Response (DOR)
Time Frame: Up to approximately 3 months after first particpant enrolled
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
Up to approximately 3 months after first particpant enrolled

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
C=cycle (cycle=28 days) ; D=day; PTFI=prior to first infusion; TDV=treatment discontinuation visit; UTA=up to approximately; M=month
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)
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)
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
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)
Objective Response Rate
Time Frame: Up to approximately 3 months after first participant enrolled
Objective response rate is defined as the percentage of participants with a partial remission (PR) or better (i.e., CR + CRp + CRi + CRh+ PR).
Up to approximately 3 months after first participant enrolled
Event-Free Survival
Time Frame: Up to approximately 3 months after first participant enrolled
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.
Up to approximately 3 months after first participant enrolled
Leukemia-Free Survival
Time Frame: Up to approximately 3 months after first participant enrolled
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.
Up to approximately 3 months after first participant enrolled
Overall Survival
Time Frame: Up to approximately 13 months after first participant enrolled
Overall survival is defined as time from study entry to the date of death from any cause.
Up to approximately 13 months after first participant enrolled
Progression-Free Survival
Time Frame: Up to approximately 3 months after first participant enrolled
Progression-free survival (Investigator) is defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.
Up to approximately 3 months after first participant enrolled
Rate of Transfusion Independence
Time Frame: Up to approximately 3 months after first participant enrolled
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.
Up to approximately 3 months after first participant enrolled
Duration of Transfusion Independence
Time Frame: Up to approximately 3 months after first participant enrolled
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.
Up to approximately 3 months after first participant enrolled
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
Baseline up to approximately 37 months
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
Baseline up to approximately 37 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 8, 2019

Primary Completion (ACTUAL)

November 3, 2020

Study Completion (ACTUAL)

November 3, 2020

Study Registration Dates

First Submitted

April 11, 2019

First Submitted That Met QC Criteria

April 17, 2019

First Posted (ACTUAL)

April 22, 2019

Study Record Updates

Last Update Posted (ACTUAL)

February 21, 2022

Last Update Submitted That Met QC Criteria

December 3, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD 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).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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