Status:
COMPLETED
Azacitidine, Venetoclax, and Trametinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndrome
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Recurrent Acute Myeloid Leukemia
Recurrent Chronic Myelomonocytic Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This phase II trial investigates how well azacitidine, venetoclax, and trametinib work in treating patients with acute myeloid leukemia or higher-risk myelodysplastic syndrome that has come back (rela...
Detailed Description
PRIMARY OBJECTIVES: I. To determine overall survival rate at 1 year of the regimen in patients with newly diagnosed acute myeloid leukemia (AML). (Cohort A) II. To determine the complete remission (C...
Eligibility Criteria
Inclusion
- Diagnosis:
- Cohort A (frontline): Newly diagnosed AML
- Cohort B (relapsed/refractory): Relapsed/refractory AML or relapsed/refractory MDS or chronic myelomonocytic leukemia (CMML) that is intermediate-2 or high-risk by the International Prognostic Scoring System with \>= 10% blasts harboring a Ras pathway-activating mutation. Eligible mutations include: activating mutations of KIT, HRAS/NRAS/KRAS, BRAF, CBL or PTPN11 or loss of function mutation of NF1. Other mutations not listed here that are anticipated to activate Ras signaling may be considered for enrollment after discussion with the principal investigator (PI)
- Performance status =\< 2 (Eastern Cooperative Oncology Group \[ECOG\] scale)
- Total serum bilirubin =\< 2.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the PI
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =\< 3 x ULN, unless due to the underlying leukemia approved by the PI
- Creatinine clearance \>= 30 mL/min
- Ability to swallow
- Signed informed consent
Exclusion
- Patients suitable for and willing to receive intensive induction chemotherapy (cohort A only)
- Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment)
- Patients with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI
- Consumed strong inducer of CYP3A or p-glycoprotein within 3 days of study enrollment. Agents include but are not limited to: carbamazepine, phenytoin, rifampin, and St. John's wart
- Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Prior recent treatment with corticosteroids, hydroxyurea and/or cytarabine (given for cytoreduction) permitted
- Pregnant women will not be eligible; women of childbearing potential should have a negative pregnancy test prior to entering on the study and be willing to practice methods of contraception throughout the study period and for at least 6 months after the last dose of study drugs. Women do not have childbearing potential if they have had a hysterectomy or are postmenopausal without menses for 12 months. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control throughout the study period and for at least 4 months after the last dose of study drugs. Lactating women (or those planning to breastfeed) should not breastfeed during treatment of trametinib and for at least 2 months after the last dose of trametinib
Key Trial Info
Start Date :
July 21 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 25 2024
Estimated Enrollment :
21 Patients enrolled
Trial Details
Trial ID
NCT04487106
Start Date
July 21 2020
End Date
January 25 2024
Last Update
April 22 2025
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
M D Anderson Cancer Center
Houston, Texas, United States, 77030