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

Conditions

• Myelodysplastic Syndromes

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab — DRUG
  Participants will receive atezolizumab as per the schedule described in individual cohort.
• Azacitidine — DRUG
  Participants will receive azacitidine as per the schedule described in individual cohort.

Study Details

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.

Key Dates

Start date

Sep 30, 2015

Status verified

Aug 2019

Primary completion

Jun 10, 2019

Completion

Jun 10, 2019

Study Design

Enrollment

46 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A: Atezolizumab - HMA R/R MDS
  Participants 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.
• Experimental: Cohort B: Atezolizumab+Azacitidine - HMA R/R MDS
  Induction: 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.
• Experimental: Cohort C1: Atezolizumab+Azacitidine - HMA-Naive MDS
  Participants 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.
• Experimental: Cohort C2: Atezolizumab+Azacitidine - HMA-Naive MDS
  If 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.
• Experimental: Cohort A2: Atezolizumab - HMA R/R MDS
  If 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.
• Experimental: Cohort B2: Atezolizumab+Azacitidine - HMA R/R MDS
  If 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.

Primary Outcome Measure

Percentage of Participants with DLTs [ Time Frame: Cohort A: Days 1 to 21; Cohorts B and C1: Days 1 to 28 ]

Locations (15)

Find similar trials in Duarte, CA

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