Geriatric Assessment & Genetic Profiling to Personalize Therapy in Older Adults With Acute Myeloid Leukemia
- Conditions
- Adult Acute Myeloid LeukemiaSecondary Acute Myeloid LeukemiaTherapy-Related Acute Myeloid Leukemia
- Interventions
- Other: Laboratory Biomarker AnalysisDrug: Liposome-encapsulated Daunorubicin-CytarabineOther: Quality-of-Life AssessmentOther: Questionnaire Administration
- Registration Number
- NCT03226418
- Lead Sponsor
- University of Nebraska
- Brief Summary
This phase II trial of the impact of clinicogenetic risk-stratified management on outcomes of acute myeloid leukemia in older patients is to determine the rate of complete remission and mortality at 90 days in the entire cohort of older patients (≥60 years) with newly diagnosed acute myeloid leukemia, who receive clinicogenetic risk-stratified therapy allocation.
Subjects will receive standard of care intensive or low-intensity induction based on cytogenetic and geriatric assessment-based risk stratification.
Subjects 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.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the rate of complete remission and mortality at 90 days in the entire cohort of older patients (\>= 60 years) with newly diagnosed acute myeloid leukemia (AML) who receive clinicogenetic risk-stratified therapy allocation.
SECONDARY OBJECTIVES:
I. To determine the rate of complete remission and mortality at 90 days in subsets of older patients who receive intensive and low-intensity chemotherapy.
II. To determine proportion of patients with impairments detected by geriatric assessment.
III. To calculate the percentage of older patients who receive allogeneic stem cell transplant during the study period IV. To assess overall survival at 1-year for the entire cohort of older patients
OUTLINE: Patients are assigned to 1 or 2 groups based on cytogenetic and geriatric assessment-based risk stratification.
GROUP I:
INTENSIVE INDUCTION THERAPY: Patients 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 are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.
INTENSIVE CONSOLIDATION THERAPY: Patients 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. Patients 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: Patients receive oral venetoclax and azacitidine IV on days 1-7 or decitabine IV on days 1-5. Alternate standard of care low-intensity therapies are allowed at the discretion of treating physician. Treatment repeats every 4 weeks for 1-4 courses in the absence of disease progression or unacceptable toxicity.
LOW-INTENSITY CONSOLIDATION: Patients who achieve complete remission, receive oral venetoclax and azacitidine IV on days 1-7 or decitabine IV on days 1-5 or other standard of care low-intensity chemotherapy. Treatment repeats every 4 weeks for 3 or more courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
After completion of study treatment, patients are followed up for up to 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group I Questionnaire Administration INTENSIVE INDUCTION THERAPY: Patients 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 are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity. INTENSIVE CONSOLIDATION THERAPY: Patients 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. Patients 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, unacceptable toxicity. Group I Cytarabine INTENSIVE INDUCTION THERAPY: Patients 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 are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity. INTENSIVE CONSOLIDATION THERAPY: Patients 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. Patients 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, unacceptable toxicity. Group I Laboratory Biomarker Analysis INTENSIVE INDUCTION THERAPY: Patients 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 are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity. INTENSIVE CONSOLIDATION THERAPY: Patients 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. Patients 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, unacceptable toxicity. Group I Liposome-encapsulated Daunorubicin-Cytarabine INTENSIVE INDUCTION THERAPY: Patients 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 are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity. INTENSIVE CONSOLIDATION THERAPY: Patients 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. Patients 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, unacceptable toxicity. Group I Quality-of-Life Assessment INTENSIVE INDUCTION THERAPY: Patients 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 are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity. INTENSIVE CONSOLIDATION THERAPY: Patients 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. Patients 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, unacceptable toxicity. Group II Laboratory Biomarker Analysis LOW-INTENSITY: Patients 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 FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib. Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily. Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 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 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Group II Quality-of-Life Assessment LOW-INTENSITY: Patients 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 FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib. Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily. Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 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 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Group II Questionnaire Administration LOW-INTENSITY: Patients 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 FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib. Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily. Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 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 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Group II Azacitidine LOW-INTENSITY: Patients 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 FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib. Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily. Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 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 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Group II glasdegib LOW-INTENSITY: Patients 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 FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib. Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily. Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 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 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Group I Idarubicin INTENSIVE INDUCTION THERAPY: Patients 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 are added to 7+3 as per the standard of care. Treatment continues for 1 course in the absence of unacceptable toxicity. INTENSIVE CONSOLIDATION THERAPY: Patients 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. Patients 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, unacceptable toxicity. Group II Decitabine LOW-INTENSITY: Patients 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 FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib. Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily. Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 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 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant. Group II Venetoclax LOW-INTENSITY: Patients 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 FLT3 inhibitor such as midostaurin, low-dose cytarabine in combination with glasdegib. Venetoclax dose varies depending on drug interaction with antifungal agents. Given daily continuous for \>= 3 months orally. Glasdegib dose is 100 mg oral daily. Decitabine IV over 1-3 hours daily for 5-10 days. Treatment repeats every 4-5 weeks for \>= 3 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 courses in the absence of disease progression, unacceptable toxicity or receipt of allogeneic stem cell transplant.
- Primary Outcome Measures
Name Time Method Rate of complete remission and mortality in the entire cohort of older patients At 90 days 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.
- Secondary Outcome Measures
Name Time Method Rate of complete remission and mortality in subsets of older patients who receive intensive and low-intensity chemotherapy At 90 days 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.
Baseline functional status measure by geriatric assessment At 90 days Will assess the impact of baseline functional status on the rate of complete remission and mortality.
Baseline functional status Up to 90 days Will evaluate the influence of baseline functional status on the quality of life and neurocognitive status. The association between categories of functional status and quality of life will be explored using analysis of variance (ANOVA); if assumptions of ANOVA fail, Kruskal Wallis will be used. The association between functional status (fit or vulnerable) and neurocognitive status (\< 25 or 26 or higher) will be explored using a chi-square test. A generalized linear mixed model will be utilized to evaluate changes in quality of life over time. The proportion (and associated 95% confidence interval) of patients with definitely or probably modifiable impairments will be presented.
Symptom burden Up to 90 days following initiation of chemotherapy Will determine the symptom burden at diagnosis and 10, 30 and 90 days following initiation of chemotherapy.
Mortality From the time of diagnosis to death, assessed up to 90 days Mortality at 90 days will be calculated as the time from date of diagnosis to date of death due to any cause by 90 days from diagnosis.
Quality of life as measured by European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) version 3.0 Up to 4 years Composite scores, as determined by EORTC QLQ-C30 version 3.0, will be utilized to determine quality of life status. A generalized linear mixed model will be utilized to evaluate changes in quality of life over time.
Neurocognitive status as measured by the Montreal Cognitive Assessment (MoCA) Up to 4 years Composite scores, as determined by MOCA test, will be utilized to determine neurocognitive status.
Trial Locations
- Locations (1)
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States