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

NCT02892318 | Completed Phase 1

• 1 other identifier: GO30139
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 8

Brief 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). 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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants with Adverse Events

  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

  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

  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

  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

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

Secondary Outcomes (9)

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

  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

  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

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

• Overall Survival (OS)

  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

  Baseline up to approximately 32 months

Study Arms (4)

Cohort A1: Safety Cohort (Relapsed/refractory AML)

EXPERIMENTAL

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; Drug: Guadecitabine

Cohort A2: Expansion Cohort (Relapsed/refractory AML)

EXPERIMENTAL

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; Drug: Guadecitabine

Cohort A3: Safety Cohort (Previously Untreated AML)

EXPERIMENTAL

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; Drug: Guadecitabine

Cohort A4: Expansion Cohort (Previously Untreated AML)

EXPERIMENTAL

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; Drug: Guadecitabine

Interventions

Atezolizumab DRUG

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

Also known as: MPDL3280A;, Tecentriq

Cohort A1: Safety Cohort (Relapsed/refractory AML); Cohort A2: Expansion Cohort (Relapsed/refractory AML); Cohort A3: Safety Cohort (Previously Untreated AML); Cohort A4: Expansion Cohort (Previously Untreated AML)

Guadecitabine DRUG

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

Cohort A1: Safety Cohort (Relapsed/refractory AML); Cohort A2: Expansion Cohort (Relapsed/refractory AML); Cohort A3: Safety Cohort (Previously Untreated AML); Cohort A4: Expansion Cohort (Previously Untreated AML)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (8)

City of Hope

Duarte, California, 91010, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

The NewYork-Presbyterian Hospital Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

The University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

atezolizumab; guadecitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2016
• First Posted: September 8, 2016
• Study Start: October 31, 2016
• Primary Completion: December 12, 2019
• Study Completion: December 12, 2019
• Last Updated: March 13, 2020

Record last verified: 2020-03

Locations

US (8)