Study Design

Trial structure

BRIGHT AML 1003 was a randomized, phase 2 study2,3
DAURISMO (glasdegib) was studied in older, difficult-to-treat adult patients with newly diagnosed AML who were not eligible for intensive chemotherapy (N=115)2-4
Patients were considered difficult to treat based on the eligibility criteria below.
  • Patients were stratified by cytogenetic risk (good/intermediate or poor)2
  • Treatment was continued until disease progression or unacceptable toxicity2
  • To assess response, BM samples were collected at screening, on day 1 of cycle 3 and every third cycle, within 14 days of achieving initial hematologic recovery in the peripheral blood, at the end of treatment, and at investigator discretion3
*AML patients included de novo AML and sAML. sAML was defined in the trial as AML evolving from MDS or another AHD, and AML occurring after previous cytotoxic therapy or radiation.3
Response assessments included complete response (CR), complete response with incomplete blood count recovery (CRi), cytogenetic complete response, molecular complete response, morphologic leukemia-free state (MLFS), minor response (MR), partial remission (PR), partial remission with incomplete blood count recovery (PRi), and stable disease (SD).3
AHD=antecedent hematologic disorder; LVEF=left ventricular ejection fraction.
 
Objective criteria for nonintensive treatment in the BRIGHT AML 1003 trial2,3
  • 65% met ≥2 criteria for nonintensive treatment at baseline
Medical Dictionary for Regulatory Activities preferred terms for severe cardiac disease were determined by study team review of medical history. Patients may have had multiple applicable terms for severe cardiac disease (eg, LVEF <45% by multigated acquisition scan or echocardiography at screening).3
 
References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 13, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. DAURISMO Prescribing Information. New York, NY: Pfizer Inc.
  3. Data on file. Pfizer Inc., New York, NY.
  4. Klepin HD. Elderly acute myeloid leukemia: assessing risk. Curr Hematol Malig Rep. 2015;10(2):118-125.

Patient characteristics

Patients in the BRIGHT AML 1003 trial had characteristics that made them difficult to treat2-4
Key patient characteristics in the DAURISMO (glasdegib) + LDAC arm
  • The majority (61%) of patients were ≥75 years old
  • 51% had sAML
  • Approximately 28% of patients with sAML were treated with a prior HMA for MDS
  • 53% had an ECOG PS of 2
  • 32% had adverse-risk disease
  • 66% had severe cardiac disease (LVEF <45%)
  • 19% had serum creatinine >1.3 mg/dL
  • 22% had baseline bone marrow blast count <30%
*Baseline ECOG PS and baseline BM blast count were not reported for 1 patient each in the DAURISMO + LDAC arm.
Medical Dictionary for Regulatory Activities preferred terms for severe cardiac disease were determined by study team review of medical history. Patients may have had multiple applicable terms for severe cardiac disease (eg, LVEF <45% by multigated acquisition scan or echocardiography at screening).3
ELN=European LeukemiaNet; LVEF=left ventricular ejection fraction.
 
References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2020. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 13, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. DAURISMO Prescribing Information. New York, NY: Pfizer Inc.
  3. Data on file. Pfizer Inc., New York, NY.
  4. Klepin HD. Elderly acute myeloid leukemia: assessing risk. Curr Hematol Malig Rep. 2015;10(2):118-125.