Acute Myeloid Leukemia
Conditions
Keywords
AML
Brief summary
The purpose of this research study is to see if people whose Acute myeloid leukemia (AML) is being successfully treated with azacitidine or decitabine in combination with venetoclax can discontinue this chemotherapy for some period of time after a year of treatment without increasing the likelihood that their AML will return.
Interventions
DRUGAzacitidine
Standard of Care Intravenous (IV) infusion
DRUGDecitabine
Standard of Care Intravenous (IV) infusion
DRUGVenetoclax
Standard of Care PO (By Mouth)
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults 18 years of age or older at the time of obtaining informed consent. * Diagnosed with Acute Myeloid Leukemia (AML) (non-M3) as defined by 2016 World Health Organization (WHO) * Eastern Cooperative Group (ECOG) performance status score ≤ 2 * Currently on frontline therapy with HMA (azacitidine or decitabine)/VEN and achieved Complete Remission (CR)/Complete Remission with incomplete marrow recovery (CRi) with MRD negativity defined as \< 0.1% by Multiparameter Flow Cytometry (MFC) * Within 12 months of starting HMA (azacitidine or decitabine)/VEN * Ineligible for or declined allogeneic hematopoietic cell transplantation (HCT) * Ability to understand and the willingness to sign a written informed consent document * Must agree to adhere to the study visit schedule and other protocol requirements * Patients must be able to provide adequate Bone Marrow (BM) aspirate and biopsy specimens for histopathological and Measurable Residual Disease analysis during the screening procedure
Exclusion criteria
* Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of AML within 28 days, or 5 half-lives, at the start of the study. Only patients who are receiving frontline HMA (azacitidine or decitabine)/VEN are potentially eligible, but if they had received a course of hydroxyurea prior to achieving CR/CRi, this is allowed. * Any serious medical condition or uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or will place the subject at unacceptable risk if he/she participates in the study. Controlled infections or other medical conditions on long-term therapy is allowed. * Patients who harbored TP53 mutation at diagnosis * AML with extramedullary involvement including central nervous system (CNS) involvement, myeloid sarcoma, and leukemia cutis requiring directed therapy at the time of enrollment. * Patient is pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Complete Response (CR)/Complete Response with incomplete hematologic recovery (CRi) | Up to 18 Months | Rates of CR/CRi at 18 months from the time of initial CR/CRi in patients who discontinue frontline HMA (azacitidine or decitabine)/VEN (venetoclax) after achieving Measurable Residual Disease (MRD) negativity by MFC within 12 months of starting therapy. The Null hypothesis (p0) will be tested against the alternative hypothesis (p1). Null hypothesis: p0 ≤ 50% will remain in CR/CRi at 18 months from the time of initial CR/CRi Alternative hypothesis: p1 ≥ 70% will remain in CR/CRi at 18 months from the time of initial CR/CRi |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 36 Months | Overall survival will be assessed in MRD-negative patients who discontinue HMA (azacitidine or decitabine)/VEN (venetoclx). Overall Survival (OS) is defined as the length of time from the start of treatment until death due to any cause. |
| Rates to Re-Treatment | Up to 36 Months | Rates to re-treatment is defined as Measurable Residual Disease (MRD)-negative CR/CRi and CR/CRi and rates to re-treatment following molecular or morphologic relapse duration discontinuation. |
| Treatment Free Molecular Remission (TFMR) | Up to 36 Months | Defined as time from Measurable Residual Disease (MRD) negativity to first MRD positivity |
| European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30)/Quality of Life (QoL) | Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months) | EORTC-QLQ-C30/QoL consists of a 30-item subject self-report questionnaire composed of five functional scales (physical, role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/quality of life scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scale scores range from 0-100. |
| Patient Reported Outcome Measurement Information System (PROMIS) | Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months) | PROMIS scale provides response options 1-5 to indicate patient-reported health status measures for physical, mental, and social well-being. It measures concepts such as pain, fatigue, physical function, depression, anxiety, and social function. |
| EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS) | Day 1 (start of enrollment), start of Discontinuation Phase, and monthly until EOT (Up to 36 Months) | EQ-5D-5L VAS is an instrument for measuring the general health status of an individual. It consists of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scale scores range from 0-100. |
Countries
United States
Contacts
CONTACTGina Bellenger
PRINCIPAL_INVESTIGATOROnyee Chan, MD
Moffitt Cancer Center
Outcome results
None listed