Geriatric Assessment & Genetic Profiling to Personalize Therapy in Older Adults With Acute Myeloid Leukemia

Adult Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia, Therapy-Related Acute Myeloid Leukemia

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.

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. The current approach for therapy selection is largely subjective based on chronological age, performance status and/or comorbidities, and does not clearly identify patients who should undergo or forego intensive chemotherapy. The outcomes of older patients with high-risk AML can improve with enhanced risk-stratification and therapy selection strategies, and with the use of low intensity combination chemotherapy in patients who are not fit to receive intensive chemotherapy. Comprehensive geriatric assessment offers a thorough assessment of multiple health domains including comorbidities, polypharmacy, cognitive, nutritional, psychological, functional and social status. Such multidimensional assessment based on geriatric principles is an important tool that can improve risk-stratification and therapy selection in older patients. This approach provides a deeper understanding of the biological age and physical fitness of patients, and anticipated tolerance to chemotherapy. In older patients with AML, previous studies have demonstrated that comprehensive geriatric assessment uncovers significant functional impairments and predicts toxicities and overall survival. Hence, geriatric assessment is considered superior to therapy allocation based on assessment of age and performance status. Up to 75 participants newly diagnosed with AML or AML equivalents, such as myeloid sarcoma, myelodysplastic syndrome in transition to AML or high-grade treatment-related myeloid neoplasm will be enrolled and assigned to one of two groups based on cytogenetic and geriatric assessment-based risk stratification. Group I will receive intensive induction and consolidation therapy. Participants will receive cytarabine and idarubicin or liposome-encapsulated daunorubicin-cytarabine to which gemtuzumab or midostaurin will be added for one course of treatment in the absence of disease progression or unacceptable toxicity. Participants who go into remission will then receive either cytarabine or liposome-encapsulated daunorubicin-cytarabine, depending on induction therapy, for up to 4 or 8 courses in the absence of disease progression or unacceptable toxicity. Group II will receive low-intensity induction and consolidation therapy. Participants will receive oral venetoclax and azacitidine, decitabine or alternate standard of care low-intensity therapies up to four courses in the absence of disease progression or unacceptable toxicity. Participants who achieve complete remission will then receive the above treatments for three or more courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. All participants are followed up for up to 2 years after completion of treatment. Study objectives include determining the rate of complete remission and mortality at 90 days in participants who receive clinicogenetic risk-stratified therapy allocation, determining the rate of complete remission and mortality in participants who receive intensive versus low-intensity chemotherapy, determining proportion of participants with impairments detected by geriatric assessment, determining the percentage of older participants receiving allogeneic stem cell transplant during the study, and to assessing the overall survival at 1-year for the entire cohort of participants.

United States

Participants by arm