Acute Myeloid Leukemia
Conditions
Keywords
AML, Geriatric Assessment, Acute myeloid leukemia
Brief summary
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.
Detailed description
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.
Interventions
DRUGGA-directed treatment regimens
Fit, vulnerable, and frail patients will receive predefined regimens based on their GA results.
Sponsors
University of Rochester
Rising Tide Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomized 1:1 to the intervention or usual care arms using stratified randomized block design. Stratum will be defined by institution and fitness categories (fit, vulnerable, frail).
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 60 and above 2. A 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 1. AML diagnosis can be based on the World Health Organization (WHO) 2022 criteria or International Consensus Classification (ICC) 2022 criteria 2. The use of hydroxyurea, cytarabine (up to 1 gm total dose), or leukapheresis for cytoreduction is allowed 3. Patients with brief exposure to all-trans retinoic acid (ATRA), arsenic trioxide (ATO) or similar product for suspected acute promyelocytic leukemia (APL), who later turn out not to have APL, are eligible 4. The use of other cancer-directed treatments (e.g., hormonal treatment, targeted treatment, immunotherapy, radiation) other than chemotherapy for other concurrent malignancies is allowed 3. Able to provide informed consent
Exclusion criteria
1. Acute promyelocytic leukemia 2. Unwilling to complete study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment failure rate at 3 months | 3 months after treatment initiation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment failure rate at 6 months | 6 months after treatment initiation | 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 |
| Overall Response Rate | 6 months after treatment initiation | 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. |
| Overall survival | Up to 2 years after randomization | 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. |
| Event-free survival | Up to 2 years after randomization | 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. |
| Grade 3-5 toxicities | 6 months after treatment initiation | 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. |
| Unplanned hospitalizations | 6 months after treatment initiation | Number of unplanned inpatient hospitalizations during the first 6 months after treatment initiation, excluding the initial hospitalization for treatment initiation. |
| Activities of Daily Living (ADL) | Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90 | 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. |
| Instrumental Activities of Daily Living (IADL) | Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90 | 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. |
| Fall History | Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90 | Change in number of falls from baseline. More falls represent worse physical function. |
| Short Physical Performance Battery (SPPB) | Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90 | Change in SPPB total score from baseline. SPPB measures physical function and ranges from 0 to 12 (higher scores represent greater physical function). |
| Montreal Cognitive Assessment (MoCA) | Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90 | Change in MoCA total score from baseline. MoCA measure cognitive function and ranges from 0 to 30 (higher scores represent greater cognitive function). |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety | Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90 | Change in PROMIS Anxiety 4a total score from baseline. PROMIS Anxiety measures anxiety and ranges from 4 to 20 (higher scores represent greater anxiety). |
| Geriatric Depression Scale-15 (GDS-15) | Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90 | Change in GDS-15 total score from baseline. GDS-15 measures depression and ranges from 0 to 15 (higher scores represent greater depression). |
| Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) | Collected baseline, start of cycle 2 or consolidation (28 day cycle), day 90, day 180, day 360 | 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. |
| Patient Reported Toxicities | Baseline, during Cycle 1, at the start of Cycle 2 (or consolidation), Day 90, and Day 180. 28 day cycle | 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. |
Countries
United States
Contacts
CONTACTKah Poh (Melissa) Loh, MD, MS
CONTACTClinical Trials Office
Outcome results
None listed