AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1NCT02892318

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

A Phase 1 study testing Atezolizumab and Guadecitabine in people with Acute Myeloid Leukemia, run by Hoffmann-La Roche at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Atezolizumab and Guadecitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
8 sitesUnited States
Study dates
31 Oct 2016to 12 Dec 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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
Show all 26Show fewer
  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • City of Hope

    Duarte, California, 91010

  • The University of Wisconsin School of Medicine and Public Health

    Madison, Wisconsin, 53705

  • Yale University

    New Haven, Connecticut, 06511

  • The NewYork-Presbyterian Hospital Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: 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.

Being tested
Atezolizumab, Guadecitabine
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL3280A;, Tecentriq

    Atezolizumab 840 mg administered by IV infusion on Days 8 and 22 of each 28-day cycle.

  • GuadecitabineDrug

    Guadecitabine 60 mg/m^2 SC on Days 1-5 of every 28-day cycle.

Study groups in NCT02892318
Study groupRoleWhat they receive
Cohort A1: Safety Cohort (Relapsed/refractory AML)ExperimentalAn 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.
Receives: Drug: Atezolizumab; Drug: Guadecitabine
Cohort A2: Expansion Cohort (Relapsed/refractory AML)ExperimentalIf 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.
Receives: Drug: Atezolizumab; Drug: Guadecitabine
Cohort A3: Safety Cohort (Previously Untreated AML)ExperimentalIf 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.
Receives: Drug: Atezolizumab; Drug: Guadecitabine
Cohort A4: Expansion Cohort (Previously Untreated AML)ExperimentalIf 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.
Receives: Drug: Atezolizumab; Drug: Guadecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Adverse Events

    Measured: Baseline up to approximately 32 months

  2. Percentage of Participants with Complete Remission (CR) as Defined by International Working Group (IWG) 2003 and European Leukemia Net (ELN) 2010 Response Criteria

    Measured: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)

  3. Percentage of Participants with Complete Remission with Incomplete Platelet Recovery (CRp) as Defined by IWG 2003 and ELN 2010 Response Criteria

    Measured: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)

  4. Percentage of Participants with Complete Remission with Incomplete Recovery (CRi) as Defined by IWG 2003 and ELN 2010 Response Criteria

    Measured: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)

  5. Duration of Response as Defined by IWG 2003 and ELN 2010 Response Criteria

    Measured: Baseline until the date of relapse/progression or death from any cause, assessed up to approximately 32 months

Secondary outcomes (9)

  1. Percentage of Participants with Best Overall Response as Defined by IWG 2003 and ELN 2010 Response Criteria

    Measured: Baseline until the date of relapse/progression or death from any cause, assessed up to approximately 32 months

  2. Event-free Survival (EFS) as Defined by IWG 2003 and ELN 2010 Response Criteria

    Measured: Baseline until the date of induction treatment failure or relapse or death from any cause, assessed up to approximately 32 months

  3. Leukemia-free Survival (LFS) as Defined by IWG 2003 and ELN 2010 Response Criteria

    Measured: Baseline until the date of relapse or death from any cause, assessed up to approximately 32 months

  4. Overall Survival (OS)

    Measured: Baseline until death from any cause, assessed up to approximately 32 months

  5. Percentage of Participants with Minimal Residual Disease (MRD) Negativity in Participants who Achieve CR, CRp, or CRi

    Measured: Baseline up to approximately 32 months

  6. Percentage of Participants with Anti-Drug Antibody (ADA) to Atezolizumab

    Measured: 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)

  7. Serum Concentration of Atezolizumab

    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)

    Measured: Day 1 up to 32 months (detailed sample collection time points are provided in Outcome Measure Description)

  8. Plasma Concentration of Guadecitabine

    Measured: 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)

  9. Plasma Concentration of Decitabine (a Metabolite Product of Guadecitabine)

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2016 (estimated)
  2. Study start31 Oct 2016
  3. Primary completion12 Dec 2019
  4. Study completion12 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02892318
Sponsor's protocol ID
GO30139
Status last verified
Mar 2020
First submitted
2 Sep 2016
Last updated
13 Mar 2020
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab and Guadecitabine in people with Acute Myeloid Leukemia, run by Hoffmann-La Roche at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with Adverse Events (time frame: Baseline up to approximately 32 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02892318.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in