Clinical trial NCT03226418: Geriatric Assessment & Genetic Profiling to Personalize Therapy in Older Adults With Acute Myeloid Leukemia
Official title: A Phase II Study of the Impact of Clinicogenetic Risk-Stratified Management on Outcomes of Acute Myeloid Leukemia in Older Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Therapy-Related Acute Myeloid Leukemia
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-07-21
Enrollment: 75
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

1. A new diagnosis of de novo, secondary or treatment-related AML, other AML equivalent such as myeloid sarcoma, myelodysplastic syndrome in transformation to AML, or high-grade treatment-related myeloid neoplasm
2. Patients aged ≥60 years
3. Karnofsky Performance Status ≥60%
4. Subjects must be able and willingly give signed informed consent

Exclusion criteria:

1. Acute promyelocytic leukemia (APL). Patients 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 for the study.
2. Relapsed or refractory AML, who require salvage therapy
3. Prior exposure to decitabine or azacitidine will be an exclusion criterion for the use of decitabine or azacitidine alone.
4. Patients, who require urgent initiation of chemotherapy (other than debulking agent such as hydroxyurea or cyclophosphamide) due to leukemia-related emergencies such as leukostasis, or disseminated intravascular coagulopathy. Patients will not be excluded solely based on prior use of debulking agent. Prior or current use of leukapheresis will be allowed.
5. Uncontrolled serious infection at the time of enrollment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, patients do not have signs of infection progression. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
6. Uncontrolled clinically significant arrhythmia, myocardial ischemia or congestive heart failure within the past 2 weeks, that is considered by the treating physician as a contraindication for initiation of chemotherapy.
7. Ejection fraction \<45% will be an exclusion criteria for intensive chemotherapy. Such patients may receive low intensity therapy.
8. Clinically significant kidney (e.g. GFR ≤45ml/minute or Creatinine of ≥2 mg/dl) or liver dysfunction (e.g. AST/ALT and/or bilirubin ≥2 times ULN) at the time of enrollment that may prevent from safely using chemotherapy. Such patients may be allowed to receive low-intensity chemotherapy. Patients with elevated bilirubin secondary to Gilbert syndrome will not be excluded.
9. Any other condition that may not allow safe use of chemotherapy based on the clinical judgment of the treating oncologist.

Primary outcomes:
measure: Rate of complete remission and mortality in the entire cohort of older patients
timeFrame: At 90 days
Secondary outcomes:
measure: Rate of complete remission and mortality in subsets of older patients who receive intensive and low-intensity chemotherapy
timeFrame: At 90 days
measure: Baseline functional status measure by geriatric assessment
timeFrame: At 90 days
measure: Baseline functional status
timeFrame: Up to 90 days
measure: Symptom burden
timeFrame: Up to 90 days following initiation of chemotherapy
measure: Mortality
timeFrame: From the time of diagnosis to death, assessed up to 90 days
measure: 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
timeFrame: Up to 4 years
measure: Neurocognitive status as measured by the Montreal Cognitive Assessment (MoCA)
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Vijaya R Bhatt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bhatt 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.