Geriatric Assessment & Genetic Profiling to Personalize Therapy in Older Adults With Acute Myeloid Leukemia
A Phase II Study of the Impact of Clinicogenetic Risk-Stratified Management on Outcomes of Acute Myeloid Leukemia in Older Patients
3 other identifiers
interventional
75
1 country
1
Brief Summary
Acute myeloid leukemia (AML) is among the most common hematologic malignancies in adults and accounts for approximately 10,000 deaths in the United States every year. AML is commonly diagnosed in sixth or seventh decades of life. The management of AML is complex in older patients because of associated comorbidities, intolerance to high-dose chemotherapy and high-risk tumor biology. In real world practice, over one-third of patients aged 60 years and older do not receive initial chemotherapy for AML, consequently, only 10-20% of patients are alive at 3-5 years. Longer-term survival has not improved significantly in last few decades. Poor survival of older patients with AML may be improved with refined risk-stratification and therapy selection strategies, integration of principles of geriatric medicine, and use of effective but low intensity and novel therapies. This study will examine the impact of clinicogenetic risk-stratified management on outcomes of acute myeloid leukemia in older participants (≥ 60 years) with newly diagnosed acute myeloid leukemia who receive clinicogenetic risk-stratified therapy allocation. Participants will receive standard of care intensive or low-intensity induction based on cytogenetic and geriatric assessment-based risk stratification. Participants will be evaluated for disease status, survival, quality of life and neurocognitive status for 90 days and then followed for a total of 2 years for survival data.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2017
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 7, 2017
CompletedFirst Submitted
Initial submission to the registry
July 19, 2017
CompletedFirst Posted
Study publicly available on registry
July 21, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 16, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2024
CompletedResults Posted
Study results publicly available
November 5, 2025
CompletedMarch 10, 2026
May 1, 2025
6.7 years
July 19, 2017
April 8, 2025
March 5, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Rate of Complete Remission and Mortality in the Entire Cohort of Older Patients
All analyses will be performed based on intent-to-treat principle. The method of inversion will be used to generate an interval estimate for the proportion of 90-day mortality.
At 90 days
Secondary Outcomes (4)
Rate of Complete Remission (CR) or CR With Incomplete Count Recovery (CRi) and Mortality in Subsets of Older Patients Who Receive Intensive and Low-intensity Chemotherapy
At 90 days
Mortality at 90 Days
Up to 90 days from diagnosis
To Asses the Impact of Treatment Intensity on Early Mortality in Older Patients, Who Receive Risk Stratified Therapy.
30 and 90 days
To Determine Proportion of Patients With Impairments Detected by Geriatric Assessments.
Baseline
Study Arms (2)
Group I Intensive Induction and Consolidation Therapies
EXPERIMENTALIntensive Induction Therapy: Participants receive cytarabine intravenously (IV) on days 1-7 and idarubicin over 10-15 minutes on days 1-3 (7+3), or liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3 and 5. Gemtuzumab or midostaurin is added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity. Intensive Consolidation Therapy: Participants who go into remission, receive cytarabine IV over 1-3 hours twice daily (BID) on days 1, 3, and 5. Treatment repeats every 4 weeks for 2-4 courses in the absence of disease progression or unacceptable toxicity. Participants treated with liposome-encapsulated daunorubicin-cytarabine receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 5-8 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
Group II Low-intensity Induction and Consolidation Therapies
EXPERIMENTALLow-intensity: Participants receive venetoclax in combination with azacitidine or decitabine or other standard of care low-intensity therapy such as azacitidine or decitabine alone or in combination with fms-like tyrosine kinase 3 (FLT3) inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib. Venetoclax dose varies depending on drug interaction with anti-fungal agents. Given daily continuous for 3 or more months orally. Glasdegib dose is 100 mg oral daily. Decitabine intravenously (IV) over 1 - 3 hours daily for 5 - 10 days. Treatment repeats every 4 - 5 weeks for 3 or more courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Azacitidine IV infusion over 10 to 40 minutes days 1 - 7. Treatment repeats every 4 - 5 weeks for 3 or more courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
Interventions
Correlative studies
Given IV
Ancillary studies
Ancillary studies
oral tablet
oral tablet
Given IV
Given IV
Given IV
Given by infusion
Eligibility Criteria
You may qualify if:
- New diagnosis of de novo, secondary or treatment-related acute myeloid leukemia (AML), other AML equivalent such as myeloid sarcoma, myelodysplastic syndrome in transformation to AML, or high-grade treatment-related myeloid neoplasm
- years of age or older
- Karnofsky Performance Status ≥60%
- Able and willingly give signed informed consent
You may not qualify if:
- Acute promyelocytic leukemia (APL). Participants with brief exposure to all-trans retinoic acid (ATRA), arsenic trioxide (ATO) or similar product for suspected APL, who later turn out not to have APL, are eligible.
- Relapsed or refractory acute myeloid leukemia (AML) requiring salvage therapy
- Participants requiring urgent initiation of chemotherapy for leukemia-related emergencies such as leukostasis or disseminated intravascular coagulopathy Participants will not be excluded solely based on current or prior use of debulking agent (e.g., hydroxyurea or cyclophosphamide). Prior or current use of leukapheresis will be allowed.
- Uncontrolled serious infection at enrollment. Infections are considered controlled if appropriate therapy has been instituted and, at enrollment, participants do not have signs of infection progression (e.g., hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection). Persistent fever without other signs or symptoms will not be interpreted as progressing infection.
- Uncontrolled clinically significant arrhythmia, myocardial ischemia or congestive heart failure within the past 2 weeks, that is considered a contraindication for initiation of chemotherapy by the treating physician
- Clinically significant kidney (e.g., glomerular filtration rate (GFR) ≤ 45ml/minute or creatinine of ≥2 mg/dl) or liver dysfunction \[e.g., aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and/or bilirubin ≥2 times upper limit of normal (ULN)\] at enrollment that may prevent safe use of chemotherapy. These participants may be allowed to receive low-intensity chemotherapy. Participants with elevated bilirubin secondary to Gilbert syndrome will not be excluded.
- Any other condition that may not allow safe use of chemotherapy based on clinical judgment of treating oncologist
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Nebraskalead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Related Publications (3)
Bhatt VR, Wichman CS, Koll TT, Fisher AL, Wildes TM, Haddadin M, Berger AM, Armitage JO, Holstein SA, Maness LJ, Gundabolu K. A Phase II Trial of Geriatric Assessment-Guided Selection of Treatment Intensity in Older Adults With AML. Am J Hematol. 2025 Jul;100(7):1163-1172. doi: 10.1002/ajh.27694. Epub 2025 Apr 29.
PMID: 40298352DERIVEDBhatt VR, Wichman C, Koll TT, Fisher AL, Wildes TM, Berger A, Armitage JO, Holstein SA, Maness LJ, Gundabolu K. Longitudinal changes in cognitive and physical function and health-related quality of life in older adults with acute myeloid leukemia. J Geriatr Oncol. 2024 Jan;15(1):101676. doi: 10.1016/j.jgo.2023.101676. Epub 2023 Nov 24.
PMID: 38000343DERIVEDBhatt VR, Wichman C, Al-Kadhimi ZS, Koll TT, Fisher AL, Mahato RI, Hyde RK, Berger A, Armitage JO, Holstein SA, Maness LJ, Gundabolu K. Integrating geriatric assessment and genetic profiling to personalize therapy selection in older adults with acute myeloid leukemia. J Geriatr Oncol. 2022 Jul;13(6):871-874. doi: 10.1016/j.jgo.2022.04.005. Epub 2022 Apr 18.
PMID: 35450817DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Vijaya Bhatt
- Organization
- University of Nebraska Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Vijaya R Bhatt, MD
University of Nebraska
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 19, 2017
First Posted
July 21, 2017
Study Start
July 7, 2017
Primary Completion
March 16, 2024
Study Completion
October 1, 2024
Last Updated
March 10, 2026
Results First Posted
November 5, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will not share