Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT01907815|
Recruitment Status : Terminated (Lack of efficacy.)
First Posted : July 25, 2013
Results First Posted : April 6, 2018
Last Update Posted : April 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Adult Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia||Drug: Akt Inhibitor GSK2141795 Other: Laboratory Biomarker Analysis Drug: Trametinib||Phase 2|
I. To determine the proportion of patients achieving complete remission (CR) or CR with incomplete recovery of platelets (CRp) as best response within 4 cycles of therapy of trametinib in combination with GSK2141795 (Akt inhibitor GSK2141795) in acute myeloid leukemia (AML) patients with rat sarcoma (RAS) mutations.
I. To determine the disease-free survival of patients achieving CR/CRp. II. To determine the duration of response of patients achieving CR/CRp. III. To determine the toxicity profile of trametinib in combination with GSK2141795 in this patient population.
IV. To determine the biologic effects of trametinib in combination with GSK2141795 on leukemia cells.
Patients receive trametinib orally (PO) once daily (QD) and Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of MEK 1/2 Inhibitor Trametinib in Combination With AKT Inhibitor GSK2141795 in Acute Myeloid Leukemia (AML) With RAS Mutations|
|Actual Study Start Date :||October 2013|
|Actual Primary Completion Date :||January 2016|
|Actual Study Completion Date :||January 2016|
Experimental: Treatment (trametinib, Akt inhibitor GSK2141795)
Trametinib orally once daily (PO QD) and Akt inhibitor GSK2141795 PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Akt Inhibitor GSK2141795
Other: Laboratory Biomarker Analysis
- Complete Response Rate (CRR, Defined as CR+CRp) Assessed by AML 2003 Response Criteria [ Time Frame: First four cycles (16 weeks) of therapy, with evaluation after one full cycle of therapy (28 days) and up to 16 weeks for response ]Proportion of participants achieving complete remission (CR) or CR with incomplete recovery of platelets (CRp) as best response within 4 cycles of therapy. Complete Response (CR): Disappearance all clinical &/or radiologic evidence of disease. Neutrophil count ≥ 1.0x10^9/L; Platelet count ≥ 100x109/L; Normal bone marrow differential (≤ 5% blasts); No extra-medullary leukemia. Complete Remission without Platelet Recovery (CRp): Peripheral blood & bone marrow results as for CR, but platelet counts of < 100x10^9/L. Partial Remission (PR): Blood count recovery as for CR, but decrease of at least 50% in % marrow blasts to >5% to 25% in bone marrow aspirate. Morphologic leukemia-free state: Normal marrow differential (<5% blasts); neutrophil & platelet counts not considered.95% confidence interval will be estimated for the combination regimen.
- Most Frequently Reported Adverse Events (AE) [ Time Frame: AE collected continuously over 28-day cycles and up to 28 days after last dose of study drug. ]National Cancer Institute (NCI) published standardized definitions for adverse events (AEs), known as Common Terminology Criteria for Adverse Events (CTCAE), to describe the severity of organ toxicity for those receiving cancer therapy. Toxicity data is summarized by number of incidents experienced while participants were on study using most frequently reported AEs regardless of grade or relatedness as assessed by CTCAE version 4.0. Toxicity is graded as mild (Grade 1), moderate (Grade 2), severe (Grade 3), or life-threatening (Grade 4), with specific parameters according to the organ system involved. Death (Grade 5) is used for some of the criteria to denote a fatality. For full adverse event reporting see Adverse Event Section. Data collection over first four cycles (16 weeks) of therapy, with evaluation after full cycle of therapy (28 days), continuing AE collection until 28 days following last study drug dose.
- Overall Survival of Participants Achieving CR/CRp [ Time Frame: Up to 12 weeks ]Estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
- Progression Free Survival of Participants Achieving CR/CRp [ Time Frame: Up to 12 weeks ]Estimated disease-free survival period using the Kaplan-Meier method. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
- Time to Progression for Participants Achieving CR/CRp [ Time Frame: Up to 12 weeks ]Time to Progression (TTP) is defined as the length of time from the start of treatment to disease progression as measured in days for participants with complete response.
- Maximum Percentage Change in Total and Phospho-proteins [ Time Frame: Baseline to 12 weeks post therapy ]Change in total and phospho-proteins assessed by densitometric quantitative data by western blot analysis, or mean fluorescent intensities by flow cytometry and will be assessed for each patient for all time points and graphically plotted for each dose level.
- Percentage Change in Cellular Proteins [ Time Frame: Baseline to day 28 post treatment ]The 95% confidence interval will be assessed.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01907815
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|United States, Maryland|
|University of Maryland/Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Nitin Jain||M.D. Anderson Cancer Center|