This is a phase 2 randomized controlled trial to evaluate whether a geriatric assessment (GA)-guided treatment strategy reduces treatment-related toxicity and improves patient-centered outcomes compared with usual oncologist-directed care in adults aged 60 years and older with newly diagnosed AML.
Acute myeloid leukemia (AML) primarily affects older adults, yet treatment decision-making in this population remains largely inconsistent. Older adults with AML are highly heterogeneous with respect to physiologic reserve, functional status, cognition, and comorbidities, all of which strongly influence treatment tolerance and outcomes. Despite this heterogeneity, treatment decisions are often made rapidly and rely heavily on chronological age and clinician judgment, approaches that have been repeatedly shown to inadequately predict toxicity, early mortality, and functional decline. The proposed trial addresses a critical scientific question: whether a structured geriatric assessment (GA)-guided treatment strategy improves clinically meaningful outcomes compared with usual oncologist-directed care in older adults with AML. Although GA has been extensively validated as a prognostic and risk stratification tool in oncology and has improved care delivery in solid tumors, it has not been tested in a randomized controlled trial in AML, where treatment urgency, toxicity burden, and early adverse events are especially pronounced. This study therefore fills a major evidence gap at the intersection of geriatric oncology and hematologic malignancies. This multicenter, prospective, randomized controlled trial is designed to evaluate whether a geriatric assessment (GA)-guided treatment strategy improves clinically meaningful outcomes compared with usual oncologist-directed care in older adults with newly diagnosed acute myeloid leukemia (AML). Approximately 120 adults aged 60 years and older will be enrolled across 3 academic and community institutions affiliated with the Cancer and Aging Research Group (CARG). Patients will be randomized in a 1:1 ratio to either a GA-guided treatment arm or a usual-care arm, with randomization stratified by study site and GA-defined fitness category (fit, vulnerable, frail). All patients will undergo a structured GA using the Practical Geriatric Assessment recommended by the American Society of Clinical Oncology and adapted for hematologic malignancies. However, GA results will be used to guide treatment selection only for participants assigned to the intervention arm.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Fit, vulnerable, and frail patients will receive predefined regimens based on their GA results.
University of Rochester Medicine
Rochester, New York, United States
Treatment failure rate at 3 months
Treatment failure is defined as the occurrence of any of the following within 3 months after treatment initiation: disease progression or relapse, death from any cause, treatment discontinuation for any reason except logistical reasons, absence of at least one agent in the initial treatment regimen for more than 30 days following the last day of the previous treatment cycle (temporary dose interruptions and cycle delays within the 30 day window are not considered treatment failure events), or initiation of an alternative treatment regimen or addition of an agent because of clinician documented concern for lack of efficacy or disease control.
Time frame: 3 months after treatment initiation
Treatment failure rate at 6 months
Treatment failure will be assessed at 6 months (180 days) after treatment initiation and include any of the following events: • Disease progression or relapse • Death from any cause • Treatment discontinuation for any reason (except logistical) • Treatment delays, defined as: o Absence of at least one agent in the initial regimen for \>30 days following the last day of prior treatment cycle o Temporary dose interruptions and cycle delays within the 30-day window are not considered treatment failure events • Initiation of an alternative treatment regimen or addition of an agent to the initial regimen due to clinician-documented concern for lack of efficacy or disease control, including but not limited to: o Failure to achieve the expected response o Rising blast percentage or worsening cytopenias attributed to disease o Loss of a prior response
Time frame: 6 months after treatment initiation
Overall Response Rate
Best overall response from the initial treatment regimen within the first 6 months after treatment initiation. Overall response includes complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and complete remission with partial hematologic recovery (CRh), assessed according to the European LeukemiaNet (ELN) 2022 response criteria.
Time frame: 6 months after treatment initiation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Overall survival
Time from randomization to death from any cause. Participants who are alive at the time of analysis will be censored at the date they were last known to be alive.
Time frame: Up to 2 years after randomization
Event-free survival
Time from randomization to the first occurrence of failure to achieve complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh), relapse after achieving CR, CRi, or CRh, or death from any cause.
Time frame: Up to 2 years after randomization
Grade 3-5 toxicities
Proportion of participants with Grade 3 or higher nonhematologic adverse events and Grade 3 or higher neutropenia, thrombocytopenia, or anemia associated with the initial treatment regimen, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Asymptomatic laboratory abnormalities lasting 7 days or less that do not result in a dose modification or treatment hold will not be included.
Time frame: 6 months after treatment initiation
Unplanned hospitalizations
Number of unplanned inpatient hospitalizations during the first 6 months after treatment initiation, excluding the initial hospitalization for treatment initiation.
Time frame: 6 months after treatment initiation
Activities of Daily Living (ADL)
Change in Katz ADL total score from baseline. ADL measures independence in activities of daily living (including bathing, dressing, toileting, transferring, continence, and feeding). ADL ranges from 0 to 6, with higher scores representing greater independence in activities of daily living.
Time frame: Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90
Instrumental Activities of Daily Living (IADL)
Change in OARS IADL total score from baseline. IADL measures independence in instrumental activities of daily living (including using the telephone, travel, shopping, meal preparation, housework, taking medications, and handling money). IADL ranges from 0 to 14, with higher scores representing greater independence in instrumental activities of daily living.
Time frame: Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90
Fall History
Change in number of falls from baseline. More falls represent worse physical function.
Time frame: Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90
Short Physical Performance Battery (SPPB)
Change in SPPB total score from baseline. SPPB measures physical function and ranges from 0 to 12 (higher scores represent greater physical function).
Time frame: Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90
Montreal Cognitive Assessment (MoCA)
Change in MoCA total score from baseline. MoCA measure cognitive function and ranges from 0 to 30 (higher scores represent greater cognitive function).
Time frame: Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90
Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety
Change in PROMIS Anxiety 4a total score from baseline. PROMIS Anxiety measures anxiety and ranges from 4 to 20 (higher scores represent greater anxiety).
Time frame: Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90
Geriatric Depression Scale-15 (GDS-15)
Change in GDS-15 total score from baseline. GDS-15 measures depression and ranges from 0 to 15 (higher scores represent greater depression).
Time frame: Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90
Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu)
Change in FACT-Leu total score from baseline. FACT-Leu measures quality of life and is designed specifically for patients with leukemia. FACT-Leu ranges from 0 to 176, with higher scores representing better quality of life.
Time frame: Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90, day 180, day 360
Patient Reported Toxicities
Change in patient reported symptomatic toxicities measured using the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO CTCAE). Responses will be assessed longitudinally at the protocol specified assessment time points.
Time frame: Baseline, during Cycle 1, at the start of Cycle 2 (or consolidation), Day 90, and Day 180. 28 day cycle