A Study Evaluating the Safety and Pharmacology of Atezolizumab Administered in Combination With Immunomodulatory Agents in Participants With Acute Myeloid Leukemia (AML)

March 11, 2020 updated by: Hoffmann-La Roche

A Phase Ib Study Evaluating the Safety and Pharmacology of Atezolizumab (Anti-PD-L1 Antibody) Administered in Combination With Immunomodulatory Agents in Patients With Acute Myeloid Leukemia

This is a non-randomized, open-label, Phase Ib study of atezolizumab in combination with immunomodulatory agents for the treatment of participants with AML (relapsed/refractory and treatment-naive, elderly participants unfit for induction chemotherapy). The study has been designed with the intent, over time, to study multiple combinations of atezolizumab with different immunomodulatory agents in participants with AML. The study will begin with the evaluation of the combination of atezolizumab and guadecitabine (Arm A). In the future, additional arms may be added.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale University
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10032
        • The NewYork-Presbyterian Hospital Columbia University Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • The University of Wisconsin School of Medicine and Public Health

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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
  • Diagnosis of AML per World Health Organization criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
  • Specifically, for participants in Cohorts A1 and A2: Age greater than or equal to (>=) 18 years, disease progression or failure to achieve complete or partial response after intensive cytotoxic therapy, participants cannot have received more than two prior intensive regimens (e.g., induction + consolidation and one salvage therapy + consolidation)
  • Specifically, for participants in Cohorts A3 and A4: Treatment naïve participants unfit for induction chemotherapy for AML as defined by the following: Age >= 70 or age 65 to 69 years with at least one of the following: ECOG performance status of 2, Intermediate I/II or adverse risk cytogenetic and molecular alterations per ELN 2010 guidelines or secondary AML, or other comorbidity judged incompatible with intensive chemotherapy
  • Adequate end-organ function
  • Willing and able to undergo a pre-treatment bone marrow aspirate and biopsy and subsequent bone marrow aspirates and biopsies during treatment
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 30 days after the last dose of guadecitabine or 5 months after the last dose of atezolizumab, whichever is longer
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

  • In Cohorts A3 and A4 only, participants with AML eligible for standard intensive induction therapy with an anthracycline and cytarabine
  • Prior allogeneic stem cell transplant or solid organ transplant
  • Active central nervous system involvement by leukemia
  • Pregnant or lactating, or intending to become pregnant during the study
  • History of idiopathic pulmonary fibrosis, organizing pneumonitis, drug-induced pneumonitis, idiopathic pneumonitis, or autoimmune disease
  • Treatment with investigational therapy within 14 days prior to initiation of study drug
  • Any approved AML-related therapy within 14 days prior to enrollment
  • Immunosuppressive therapy within 6 weeks of Cycle 1, Day 1
  • Daily requirement for corticosteroids (> 10 mg prednisone daily or equivalent) (except for inhalation corticosteroids) within 2 weeks prior to Cycle 1, Day 1
  • Prior treatment with immune checkpoint blockade therapies (anti-cytotoxic T-lymphocyte-associated protein 4 [anti-CTLA-4], anti-programmed death-1 [anti-PD-1] or anti-PD-L1) or immune agonists (anti-cluster of differentiation [CD]137, anti-CD40, anti-OX40)
  • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to Cycle 1, Day 1
  • Treatment with denosumab (or other receptor activator of nuclear factor kappa-B ligand [RANKL] inhibitor) 4 weeks before the first dose and for 10 weeks after the last dose of atezolizumab
  • Administration of a live, attenuated vaccine within 4 weeks of Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • Planned major surgery during the study
  • Positive for hepatitis C virus (HCV) antibody at screening
  • Active hepatitis B virus (HBV) infection
  • Positive for human immunodeficiency virus (HIV)
  • Illicit drug or alcohol abuse within 12 months prior to screening
  • Poor peripheral venous access
  • Active infection
  • Serious infection requiring hospitalization or intravenous (IV) antibiotics within 14 days prior to enrollment
  • Any serious medical condition or abnormality in clinical laboratory tests
  • History or presence of an abnormal electrocardiogram (ECG)
  • History of other malignancy within 2 years prior to screening
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab or guadecitabine formulations
  • History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

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: NON_RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Cohort A1: Safety Cohort (Relapsed/refractory AML)
An initial safety evaluation of the combination will be performed in 9 participants with relapsed/refractory AML. All participants will receive atezolizumab (840 milligrams [mg] IV on Days 8 and 22 of every 28-day cycle) administered in combination with guadecitabine (60 milligrams per square meter [mg/m^2] subcutaneously [SC] on Days 1-5 of every 28-day cycle). Treatment with both study drugs will continue until loss of clinical benefit (except in participants who achieve a CR, CRp, or CRi), evidence of unacceptable toxicity, voluntary withdrawal from the study, study termination, or death, whichever occurs first. Participants who achieve a CR, CRp, or CRi will receive an additional six cycles of the combination as consolidation treatment. Participants will discontinue therapy at the end of consolidation response assessment even if the CR, CRp, or CRi is maintained at that time.
Drug: Atezolizumab
Atezolizumab 840 mg administered by IV infusion on Days 8 and 22 of each 28-day cycle.
Other Names:
  • Tecentriq
  • MPDL3280A;
Drug: Guadecitabine
Guadecitabine 60 mg/m^2 SC on Days 1-5 of every 28-day cycle.
EXPERIMENTAL: Cohort A2: Expansion Cohort (Relapsed/refractory AML)
If the combination of atezolizumab and guadecitabine is found to be safe and tolerable in Cohort A1, an expansion cohort of 11 participants with relapsed/refractory AML (Cohort A2) will be evaluated. All participants will receive atezolizumab (840 mg IV on Days 8 and 22 of every 28-day cycle) administered in combination with guadecitabine (60 mg/m^2 SC on Days 1-5 of every 28-day cycle). Treatment with both study drugs will continue until loss of clinical benefit except in participants who achieve a CR, CRp, or CRi), evidence of unacceptable toxicity, voluntary withdrawal from the study, study termination, or death, whichever occurs first. Participants who achieve a CR, CRp, or CRi will receive an additional six cycles of the combination as consolidation treatment. Participants will discontinue therapy at the end of consolidation response assessment even if the CR, CRp, or CRi is maintained at that time.
Drug: Atezolizumab
Atezolizumab 840 mg administered by IV infusion on Days 8 and 22 of each 28-day cycle.
Other Names:
  • Tecentriq
  • MPDL3280A;
Drug: Guadecitabine
Guadecitabine 60 mg/m^2 SC on Days 1-5 of every 28-day cycle.
EXPERIMENTAL: Cohort A3: Safety Cohort (Previously Untreated AML)
If the combination of atezolizumab and guadecitabine is found to be safe and tolerable in Cohort A1, Cohort A3 will assess the safety and tolerability of the combination in 6 participants with untreated AML, who are older and unfit for induction chemotherapy. All participants will receive atezolizumab (840 mg IV on Days 8 and 22 of every 28-day cycle) administered in combination with guadecitabine (60 mg/m^2 SC on Days 1-5 of every 28-day cycle). Treatment with both study drugs will continue until loss of clinical benefit except in participants who achieve a CR, CRp, or CRi), evidence of unacceptable toxicity, voluntary withdrawal from the study, study termination, or death, whichever occurs first. Participants who achieve a CR, CRp, or CRi will receive an additional six cycles of the combination as consolidation treatment. Participants will discontinue therapy at the end of consolidation response assessment even if the CR, CRp, or CRi is maintained at that time.
Drug: Atezolizumab
Atezolizumab 840 mg administered by IV infusion on Days 8 and 22 of each 28-day cycle.
Other Names:
  • Tecentriq
  • MPDL3280A;
Drug: Guadecitabine
Guadecitabine 60 mg/m^2 SC on Days 1-5 of every 28-day cycle.
EXPERIMENTAL: Cohort A4: Expansion Cohort (Previously Untreated AML)
If Cohort A3 is deemed safe and tolerable, an expansion cohort (Cohort A4) of 14 participants with untreated AML, who are older and unfit for induction chemotherapy will be evaluated. All participants will receive atezolizumab (840 mg IV on Days 8 and 22 of every 28-day cycle) administered in combination with guadecitabine (60 mg/m^2 SC on Days 1-5 of every 28-day cycle). Treatment with both study drugs will continue until loss of clinical benefit except in participants who achieve a CR, CRp, or CRi), evidence of unacceptable toxicity, voluntary withdrawal from the study, study termination, or death, whichever occurs first. Participants who achieve a CR, CRp, or CRi will receive an additional six cycles of the combination as consolidation treatment. Participants will discontinue therapy at the end of consolidation response assessment even if the CR, CRp, or CRi is maintained at that time.
Drug: Atezolizumab
Atezolizumab 840 mg administered by IV infusion on Days 8 and 22 of each 28-day cycle.
Other Names:
  • Tecentriq
  • MPDL3280A;
Drug: Guadecitabine
Guadecitabine 60 mg/m^2 SC on Days 1-5 of every 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of Participants with Adverse Events
Time Frame: Baseline up to approximately 32 months
Baseline up to approximately 32 months
Percentage of Participants with Complete Remission (CR) as Defined by International Working Group (IWG) 2003 and European Leukemia Net (ELN) 2010 Response Criteria
Time Frame: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
Percentage of Participants with Complete Remission with Incomplete Platelet Recovery (CRp) as Defined by IWG 2003 and ELN 2010 Response Criteria
Time Frame: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
Percentage of Participants with Complete Remission with Incomplete Recovery (CRi) as Defined by IWG 2003 and ELN 2010 Response Criteria
Time Frame: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
Duration of Response as Defined by IWG 2003 and ELN 2010 Response Criteria
Time Frame: Baseline until the date of relapse/progression or death from any cause, assessed up to approximately 32 months
Baseline until the date of relapse/progression or death from any cause, assessed up to approximately 32 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants with Best Overall Response as Defined by IWG 2003 and ELN 2010 Response Criteria
Time Frame: Baseline until the date of relapse/progression or death from any cause, assessed up to approximately 32 months
Baseline until the date of relapse/progression or death from any cause, assessed up to approximately 32 months
Event-free Survival (EFS) as Defined by IWG 2003 and ELN 2010 Response Criteria
Time Frame: Baseline until the date of induction treatment failure or relapse or death from any cause, assessed up to approximately 32 months
Baseline until the date of induction treatment failure or relapse or death from any cause, assessed up to approximately 32 months
Leukemia-free Survival (LFS) as Defined by IWG 2003 and ELN 2010 Response Criteria
Time Frame: Baseline until the date of relapse or death from any cause, assessed up to approximately 32 months
Baseline until the date of relapse or death from any cause, assessed up to approximately 32 months
Overall Survival (OS)
Time Frame: Baseline until death from any cause, assessed up to approximately 32 months
Baseline until death from any cause, assessed up to approximately 32 months
Percentage of Participants with Minimal Residual Disease (MRD) Negativity in Participants who Achieve CR, CRp, or CRi
Time Frame: Baseline up to approximately 32 months
Baseline up to approximately 32 months
Percentage of Participants with Anti-Drug Antibody (ADA) to Atezolizumab
Time Frame: Pre-infusion (0 hours [hrs]) on Day (D) 1 of Cycle (C) 1; D8 of C2, C3, C4, C6, and every 6 cycles thereafter until treatment discontinuation (up to 32 months); at 120 days and 1 year after atezolizumab last dose (up to 32 months; each cycle is 28 days)
Pre-infusion (0 hours [hrs]) on Day (D) 1 of Cycle (C) 1; D8 of C2, C3, C4, C6, and every 6 cycles thereafter until treatment discontinuation (up to 32 months); at 120 days and 1 year after atezolizumab last dose (up to 32 months; each cycle is 28 days)
Serum Concentration of Atezolizumab
Time Frame: Day 1 up to 32 months (detailed sample collection time points are provided in Outcome Measure Description)
Pre-infusion (0 hrs) on D1 of C1, C4; 30 minutes after end of infusion (infusion duration=30-60 minutes) on D8 of C1, C2, C4; Pre infusion (0 hrs) on D22 of C1, D8 of C2, C3, C4, C6, every 6 cycles thereafter until treatment discontinuation (up to 32 months); at 120 days and 1 year after atezolizumab last dose (up to 32 months; each cycle is 28 days)
Day 1 up to 32 months (detailed sample collection time points are provided in Outcome Measure Description)
Plasma Concentration of Guadecitabine
Time Frame: 1, 2, 5, and 8 hours post-injection on D1 of C1 and C4, 1 hour post-injection on D1 of C2, C3, C6, and every 6 cycles thereafter (up to 32 months; each cycle is 28 days)
1, 2, 5, and 8 hours post-injection on D1 of C1 and C4, 1 hour post-injection on D1 of C2, C3, C6, and every 6 cycles thereafter (up to 32 months; each cycle is 28 days)
Plasma Concentration of Decitabine (a Metabolite Product of Guadecitabine)
Time Frame: 1, 2, 5, and 8 hours post-injection on D1 of C1 and C4, 1 hour post-injection on D1 of C2, C3, C6, and every 6 cycles thereafter (up to 32 months; each cycle is 28 days)
1, 2, 5, and 8 hours post-injection on D1 of C1 and C4, 1 hour post-injection on D1 of C2, C3, C6, and every 6 cycles thereafter (up to 32 months; each cycle is 28 days)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 31, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 12, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 12, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 2, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 8, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 13, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GO30139

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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