Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT03190915|
Recruitment Status : Recruiting
First Posted : June 19, 2017
Last Update Posted : June 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Activating RAS Mutation Juvenile Myelomonocytic Leukemia Monosomy 7 Neurofibromatosis Type 1 NF1 Gene Mutation PTPN11 Gene Mutation Splenomegaly||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Trametinib||Phase 2|
I. To determine the objective response rate to trametinib in children with recurrent or refractory juvenile myelomonocytic leukemia (JMML).
I. To further define and describe the toxicities of single agent trametinib in children with recurrent or refractory JMML.
II. To further characterize the pharmacokinetics of trametinib in children with recurrent or refractory JMML.
III. To prospectively evaluate mutant allele burden as a marker of disease activity in JMML.
IV. To measure the objective response rate to 12 cycles of trametinib in children with recurrent or refractory JMML.
I. To describe the distribution of JMML diagnostic criteria in children with recurrent or refractory JMML.
Patients receive trametinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up annually for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of the MEK Inhibitor Trametinib in Children With Relapsed or Refractory Juvenile Myelomonocytic Leukemia|
|Actual Study Start Date :||October 6, 2017|
|Estimated Primary Completion Date :||December 30, 2020|
|Estimated Study Completion Date :||December 30, 2020|
Experimental: Treatment (trametinib)
Patients receive trametinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Objective response [ Time Frame: Up to 4 courses ]Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.
- Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to course 12 ]Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade.
- Pharmacokinetic parameters of trametinib [ Time Frame: Up to course 12 ]A descriptive analysis of pharmacokinetic parameters of trametinib will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Mutant allele burden measured by mass spectrometry [ Time Frame: Up to course 12 ]Will be analyzed descriptively. Values will be summarized with means, standard deviations, and 95% confidence intervals.
- Trametinib concentrations measured by mass spectrometry [ Time Frame: Up to course 12 ]Will be analyzed descriptively. Values will be summarized with means, standard deviations, and 95% confidence intervals.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03190915
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|Principal Investigator:||Elliot Stieglitz||Children's Oncology Group|