Minimal Residual Disease, Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia
Conditions
Keywords
Venetoclax, Hypomethylation agent, Cytarabine
Brief summary
Although studies are ongoing to evaluate the efficiency and safety of venetoclax-based therapy, alone or in combination with hypomethylation agent or low-dose cytarabine, in relapsed/refractory acute myeloid leukemia, data are scarce and heterogenous. In this study, the investigators aimed to assess safety and response to a new venetoclax-based triple-drug combination regimen (venetoclax + hypomethylation agent + low-dose cytarabine) in acute myeloid leukemia patients who had relapsed/refractory disease or positive minimal residual disease.
Detailed description
Although the promising activity of venetoclax-based therapy is well demonstrated in the treatment of previously untreated elderly or unfit patients with acute myeloid leukemia, there are few data on the efficacy of venetoclax-based salvage therapy in relapsed/refractory patients, which can be difficult to treat. To date, data on venetoclax as monotherapy or in combination with hypomethylation agent or low-dose cytarabine as a salvage regimen in relapsed/refractory AML are scarce and heterogenous. In this study, the investigators aimed to assess safety and efficiency of a new triple-drug combination regimen, venetoclax + hypomethylation agent + low-dose cytarabine, in patients with relapsed/refractory acute myeloid leukemia or persistent positive minimal residual disease in the salvage setting.
Interventions
DRUGVenetoclax, Decitabine, Azacytidine, Cytarabine
Venetoclax was given at a dose of 400 mg/day for 28 days per cycle. Decitabine was given at a dose of 20 mg/m2/day for 5 days (n=3) or azacytidine (n=8) was given at a dose of 75 mg/m2/day for 7 days at the discretion of the treating physician. Cytarabine was given at a dose of 10 mg/m2 twice daily for 7 days.
Sponsors
Beijing 302 Hospital
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
1. Aged ≥18 years old, voluntarily participate in clinical research and sign an informed consent form and be willing to follow and be able to complete all experimental procedures. 2. The toxic and side effects caused by the last treatment should be recovered. 3. Eastern Cooperative Oncology Group score of 0 to 3 points. 4. The organ function is intact. * Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (Upper Limit of Normal). * Creatinine≤1.5×ULN. * Bilirubin≤1.5×ULN. 5. Karnofsky≥70. 6. The expected survival period is at least 12 weeks. 7. Non-pregnant, non-breastfeeding women.
Exclusion criteria
1. Suffering from other untreated or unrelieved malignant tumors within 2 years. 2. Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication. 3. Suffering from any other known serious and/or uncontrolled disease (eg, uncontrolled diabetes; cardiovascular disease, including congestive heart failure New York Heart Association \[NYHA\] Class III or IV, 6 months patients with myocardial infarction and poorly controlled blood pressure); chronic renal failure; or active uncontrolled infection); the investigators considered unsuitable for this clinical trial. 4. Patients who are unwilling or unable to comply with the protocol. 5. Currently being treated with other systemic anti-tumor or anti-tumor research drugs. 6. Women who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate | At the end of Cycle 2 (each cycle is 28 days) | percentage of subjects with complete remission (CR) and incomplete hematologic recovery (CRi) |
| Complete minimal residual disease (MRD) Response Rate | At the end of Cycle 2 (each cycle is 28 days) | Percentage of subjects with MRD negative or MRD \< 0.01% |
| MRD Response Rate | At the end of Cycle 2 (each cycle is 28 days) | Percentage of subjects with MRD \< 0.1% detectable by multicolor flow cytometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-Free Survival | 24 months | Time interval from leukemia free state to the first recurrence or death |
| Adverse events | start of treatment to 2 weeks after end of treatment | Number of subjects with adverse events |
| Overall Survival | 24 months | Time interval from start of treatment until death or last follow-up |
| Duration of response | 24 months | Time interval from morphologic/MRD response to loss of response or death |
Contacts
Primary ContactXiao-ning Gao
Backup ContactLei Xu
Outcome results
None listed