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Myelodysplastic SyndromesPhase 1NCT02508870

A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes

A Phase 1 study testing Atezolizumab and Azacitidine in people with Myelodysplastic Syndromes, run by Hoffmann-La Roche at 15 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 multicenter, open-label, Phase 1b study of atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1] monoclonal antibody) in participants who have hypomethylating agent (HMA)-naïve myelodysplastic syndromes (MDS) and are International Prognostic Scoring System-Revised (IPSS-R) intermediate/high/very… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Atezolizumab and Azacitidine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
15 sitesUnited States
Study dates
30 Sep 2015to 10 Jun 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

  • Diagnosis of MDS (participants with therapy-related MDS are eligible)
  • Eastern Cooperative Oncology Group (ECOG) performance status score less than or equal to (</=) 2
  • Adequate end-organ function, as determined by laboratory tests obtained within 28 days prior to the first dose of study drug
  • Willing and able to undergo a pre-treatment bone marrow biopsy and subsequent on-treatment bone marrow biopsies
  • Women who are not postmenopausal or surgically sterile must have a negative serum pregnancy test result within 28 days prior to initiation of study drug
  • For women of childbearing potential and men: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive measures
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  • For participants in Cohorts A, A2, B, and B2:
  • Progression at any time after initiation of azacitidine or decitabine treatment OR
  • Failure to achieve complete or partial response or hematological improvement after at least six 4-week cycles of azacitidine or either four 4-week or four 6-week cycles of decitabine OR
  • Relapse after initial complete or partial response or hematological improvement after six 4-week cycles of azacitidine or either four 4-week or four 6-week cycles of decitabine administered within the past 2 years
  • For participants in Cohorts C1 and C2:
  • Must not have received prior treatment for MDS with any hypomethylating agent
  • IPSS-R risk category of Intermediate, High, or Very High assessed at screening

Who cannot join

  • Participants with a diagnosis of MDS secondary to paroxysmal nocturnal hemoglobinuria (PNH), aplastic anemia, or another inherited bone marrow failure disorder
  • Prior allogeneic stem cell transplant or solid organ transplant
  • Pregnant or lactating, or intending to become pregnant during the study
  • Investigational therapy within 28 days prior to initiation of study treatment
  • Immunosuppressive therapy within 6 weeks of Cycle 1, Day 1
  • Prior treatment with immune checkpoint blockade therapies (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed death-1 [PD-1] or anti-PD-L1) or immune agonists (anti-cluster of differentiation [CD] 137, anti-CD40, anti-OX40)
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  • Any other therapy or serious medical condition, as specified in the protocol, or abnormality in clinical laboratory tests that, in the investigator's judgement, precludes the participant's safe participation in and completion of the study
  • Left ventricular ejection fraction (LVEF) </= 40 percent (%) at screening
  • Planned major surgery during the study or within 4 weeks of Cycle 1, Day 1
  • History of idiopathic pulmonary fibrosis, organizing pneumonitis, drug-induced pneumonitis, or idiopathic pneumonitis or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • University of Colorado Hospital - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute; Grace Cancer Drug Center

    Buffalo, New York, 14263

  • Medical University of South Carolina; Hollings Cancer Center

    Charleston, South Carolina, 29425

  • University of Virginia Health System; Hematology/Oncology Division

    Charlottesville, Virginia, 22908

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44915

  • City of Hope

    Duarte, California, 91010

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • University of Nebraska Medical Center; UNMC Oncology/Hematology

    Omaha, Nebraska, 68198-7680

  • Stanford University

    Palo Alto, California, 94305

  • University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94158

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Montefiore Einstein Cancer Center

    The Bronx, New York, 10461

  • University of Kansas Medical Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: A Phase Ib Study of the Safety and Pharmacology of Atezolizumab (Anti-PD-L1 Antibody) Administered Alone or in Combination With Azacitidine in Patients With Myelodysplastic Syndromes

This is a multicenter, open-label, Phase 1b study of atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1] monoclonal antibody) in participants who have hypomethylating agent (HMA)-naïve myelodysplastic syndromes (MDS) and are International Prognostic Scoring System-Revised (IPSS-R) intermediate/high/very high-risk, or have MDS relapsed or are refractory (R/R) to prior HMA therapy. The primary objectives of this study are to determine the safety and tolerability of atezolizumab therapy in these participant populations, including treatment in combination with azacitidine.

Medical subject headings
Myelodysplastic Syndromes

What participants receive

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

  • AtezolizumabDrug

    Also called Tecentriq, MPDL3280A, RO5541267

    Participants will receive atezolizumab as per the schedule described in individual cohort.

  • AzacitidineDrug

    Also called Vidaza

    Participants will receive azacitidine as per the schedule described in individual cohort.

Study groups in NCT02508870
Study groupRoleWhat they receive
Cohort A: Atezolizumab - HMA R/R MDSExperimentalParticipants with MDS who are HMA R/R will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion every 3 weeks (Q3W) (21-day cycle). Treatment will continue for up to 17 cycles or until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first. Participants who achieve/maintain a partial response (PR) or hematological improvement (HI) after receiving 17 cycles of therapy may continue on study treatment beyond Cycle 17 until loss of clinical benefit.
Receives: Drug: Atezolizumab
Cohort B: Atezolizumab+Azacitidine - HMA R/R MDSExperimentalInduction: Participants with MDS who are HMA R/R will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 milligrams per square meter (mg/m^2) subcutaneously (SC) on Days 1 to 7 of 28-day cycle, for 6 cycles. Maintenance: Participants who complete induction treatment will receive atezolizumab 1200 mg IV infusion Q3W (21-day cycle) for up to 8 additional cycles. Participants who achieve/maintain a PR or HI after completing the 8 cycles of atezolizumab maintenance therapy, may continue on study treatment until loss of clinical benefit.
Receives: Drug: Atezolizumab; Drug: Azacitidine
Cohort C1: Atezolizumab+Azacitidine - HMA-Naive MDSExperimentalParticipants with MDS who are HMA-naive will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m^2 SC on Days 1 to 7 of 28-day cycle, until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: Azacitidine
Cohort C2: Atezolizumab+Azacitidine - HMA-Naive MDSExperimentalIf the participants enrolled in Cohort C1 fulfil the dose limiting toxicity (DLT) criteria, then additional participants with MDS who are HMA-naïve will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m^2 SC on Days 1 to 7 of 28-day cycle, until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: Azacitidine
Cohort A2: Atezolizumab - HMA R/R MDSExperimentalIf atezolizumab alone or in combination with azacitidine is found to be initially safe and tolerable in participants with HMA R/R MDS in both Cohorts A and B, then additional randomly assigned participants will receive atezolizumab 1200 mg IV infusion Q3W (21-day cycle). Treatment will continue for up to 17 cycles or until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first. Participants who achieve/maintain a PR or HI after receiving 17 cycles of therapy may continue on study treatment beyond Cycle 17 until loss of clinical benefit.
Receives: Drug: Atezolizumab
Cohort B2: Atezolizumab+Azacitidine - HMA R/R MDSExperimentalIf atezolizumab alone or in combination with azacitidine is found to be initially safe and tolerable in participants with HMA R/R MDS in both Cohorts A and B, then additional randomly assigned participants will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m^2 SC on Days 1 to 7 of 28-day cycle, for 6 cycles during induction. Participants who complete induction treatment will receive maintenance atezolizumab 1200 mg IV infusion Q3W (21-day cycle) for up to 8 additional cycles. Participants who achieve/maintain a PR or HI after completing the 8 cycles of atezolizumab maintenance therapy, may continue on study treatment until loss of clinical benefit.
Receives: Drug: Atezolizumab; Drug: Azacitidine

What is being measured

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

  1. Percentage of Participants with DLTs

    Measured: Cohort A: Days 1 to 21; Cohorts B and C1: Days 1 to 28

  2. Recommended Phase 2 Dose (RP2D) of Atezolizumab in Combination with Azacitidine

    Measured: Cohort A: Days 1 to 21; Cohorts B and C1: Days 1 to 28

  3. Percentage of Participants with Adverse Events (AEs)

    Measured: Baseline up to approximately 3.5 years

Secondary outcomes (18)

  1. Cohorts A and A2: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab

    Measured: Pre-infusion (0 hour [0h]) on Day 1 (D1) of Cycles (Cy) 1, 2, 3, 4, 8, 12, and 16, end of treatment (EOT) (up to approximately 3.5 years [Yr]), and 90 days after last dose (up to approximately 3.5 Yr) (Cy length = 21 days)

  2. Cohorts B and B2: Percentage of Participants with ADAs to Atezolizumab

    Measured: Pre-infusion (0h) on Cy1, 2 Days 8 (D8) & 22 (D22) & Cy3 D8; pre-infusion (0h) on Cy7 D1 & then every 8 Cy up to EOT (approximately 3.5 Yr) and 90 days after last dose (approximately 3.5 Yr) (Cy length = 21 or 28 days)

  3. Cohorts C1 and C2: Percentage of Participants with ADAs to Atezolizumab

    Measured: Pre-infusion (0h) on Cy1, 2 D8 & D22 & Cy3 D8; pre-infusion (0h) on Cy7 D8 & then every 8 Cy up to EOT (approximately 3.5 Yr) and 90 days after last dose (approximately 3.5 Yr) (Cy length = 21 or 28 days)

  4. Cohorts A and A2: Maximum Serum Concentration (Cmax) of Atezolizumab

    Measured: Pre-infusion (0h), 30 minutes (min) post 60-min infusion on Cy 1 D1; pre-infusion (0h) on D1 of Cy 2, 3, 4, 8, 12, & 16, EOT (approximately 3.5 Yr); 90 days after EOT (approximately 3.5 Yr) (Cy length = 21 days)

  5. Cohorts B and B2: Cmax of Atezolizumab

    Measured: Pre-infusion (0h), 30 min post 60-min infusion on Cy1D8; pre-infusion (0h) on Cy1D22, Cy2D8 & 22, Cy3D8, Cy7D1, every 8 Cy up to EOT (approximately 3.5 Yr); 90 days after EOT (approximately 3.5 Yr) (1 Cy = 21 or 28 days)

  6. Cohorts C1 and C2: Cmax of Atezolizumab

    Measured: Pre-infusion (0h), 30 min post 60-min infusion on Cy1D8; pre-infusion (0h) on Cy1D22, Cy2D8 & 22, Cy3D8, Cy7D8, every 8 Cy up to EOT (approximately 3.5 Yr); 90 days after EOT (approximately 3.5 Yr) (1 Cy = 21 or 28 days)

  7. Cohorts A and A2: Minimum Serum Concentration (Cmin) of Atezolizumab

    Measured: Pre-infusion (0h), 30 minutes (min) post 60-min infusion on Cy 1 D1; pre-infusion (0h) on D1 of Cy 2, 3, 4, 8, 12, & 16, EOT (approximately 3.5 Yr); 90 days after EOT (approximately 3.5 Yr) (Cy length = 21 days)

  8. Cohorts B and B2: Cmin of Atezolizumab

    Measured: Pre-infusion (0h), 30 min post 60-min infusion on Cy1D8; pre-infusion (0h) on Cy1D22, Cy2D8 & 22, Cy3D8, Cy7D1, every 8 Cy up to EOT (approximately 3.5 Yr); 90 days after EOT (approximately 3.5 Yr) (1 Cy = 21 or 28 days)

  9. Cohorts C1 and C2: Cmin of Atezolizumab

    Measured: Pre-infusion (0h), 30 min post 60-min infusion on Cy1D8; pre-infusion (0h) on Cy1D22, Cy2D8 & 22, Cy3D8, Cy7D8, every 8 Cy up to EOT (approximately 3.5 Yr); 90 days after EOT (approximately 3.5 Yr) (1 Cy = 21 or 28 days)

  10. Percentage of Participants with Overall Response, According to 2006 International Working Group (IWG) Response Criteria for MDS

    Measured: Randomization up to disease progression or death, whichever occurs first (up to approximately 3.5 years)

  11. Percentage of Participants with Overall Response After Induction Therapy, According to 2006 IWG Response Criteria for MDS

    Measured: After end of induction up to disease progression or death, whichever occurs first (up to approximately 3.5 years)

  12. Duration of Clinical Response, According to 2006 IWG Response Criteria for MDS

    Measured: Time from the initial overall response to the time of disease progression or death, whichever occurs first (up to approximately 3.5 years)

  13. Time to Acute Myeloid Leukemia (AML) Progression, According to 2006 IWG Response Criteria for MDS

    Measured: Randomization up to the date of AML progression (up to approximately 3.5 years)

  14. Progression Free Survival (PFS), According to 2006 IWG Response Criteria for MDS

    Measured: Randomization up to disease progression or death, whichever occurs first (up to approximately 3.5 years)

  15. Cohorts A, A2, B, and B2: Overall Survival (OS)

    Measured: Randomization up to death due to any cause (up to approximately 3.5 years)

  16. Percentage of Participants With Change in Red Cell and Platelet Transfusion

    Measured: Baseline up to approximately 3.5 years

  17. Cohorts A2 or B2: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score

    Measured: D1 of every Cy up to study discontinuation (approximately 3.5 Yr) (1 Cy = 21 or 28 days)

  18. Cohorts A2 and B2: Functional Assessment of Chronic Illness Therapy Fatigue Questionnaire (FACIT-Fatigue) Score

    Measured: D1 of every Cy up to study discontinuation (approximately 3.5 Yr) (1 Cy = 21 or 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 posted27 Jul 2015 (estimated)
  2. Study start30 Sep 2015
  3. Primary completion10 Jun 2019
  4. Study completion10 Jun 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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02508870
Sponsor's protocol ID
GO29754
Status last verified
Aug 2019
First submitted
24 Jul 2015
Last updated
19 Aug 2019
Results posted
No

Publications

  • Gerds AT, Scott BL, Greenberg P, Lin TL, Pollyea DA, Verma A, Dail M, Feng Y, Green C, Ma C, Medeiros BC, Yan M, Yousefi K, Donnellan W. Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome. Blood Adv. 2022 Feb 22;6(4):1152-1161. doi: 10.1182/bloodadvances.2021005240.

    PubMed 34932793

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab and Azacitidine in people with Myelodysplastic Syndromes, run by Hoffmann-La Roche at 15 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 13 inclusion and 10 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 19 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 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 DLTs (time frame: Cohort A: Days 1 to 21; Cohorts B and C1: Days 1 to 28). The study lists 3 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 NCT02508870, which also lists 1 linked publication.

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 19 Aug 2019.

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