LCL161 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis
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|ClinicalTrials.gov Identifier: NCT02098161|
Recruitment Status : Completed
First Posted : March 27, 2014
Last Update Posted : June 1, 2022
|Condition or disease||Intervention/treatment||Phase|
|Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase Primary Myelofibrosis Secondary Myelofibrosis||Other: Laboratory Biomarker Analysis Other: Questionnaire Administration Drug: Smac Mimetic LCL161||Phase 2|
I. To determine the efficacy of LCL161 as therapy for primary myelofibrosis (PMF), post-polycythemia vera (PV) myelofibrosis (MF) and post-essential thrombocytosis (ET) MF.
II. To determine the objective response which is defined as CR (complete remission) + PR (partial remission) + CI (clinical improvement) after three cycles of treatment.
I. To determine the safety of LCL161 as therapy for PMF, post-PV MF and post-ET MF.
II. To determine time to response and response duration. III. To assess changes in symptom burden as assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) and M.D. Anderson Symptom Inventory (MDASI) questionnaires.
I. To assess the mechanisms of action of LCL161 in patients with MF; these studies will include the analysis of baculoviral IAP repeat containing 2 (cIAP1), X-linked inhibitor of apoptosis, E3 ubiquitin protein ligase (XIAP), and poly (adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP) protein levels which will be determined by western blot (actin as loading control) and will be measured at baseline and at beginning of each cycle for first 3 cycles and at end of study.
Patients receive SMAC mimetic LCL161 orally (PO) on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open Label Phase 2 Single Agent Study of LCL-161 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)|
|Actual Study Start Date :||December 18, 2014|
|Actual Primary Completion Date :||May 19, 2022|
|Actual Study Completion Date :||May 19, 2022|
Experimental: Treatment (SMAC mimetic LCL161)
Patients receive SMAC mimetic LCL161 PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration
Drug: Smac Mimetic LCL161
Other Name: LCL161
- Objective response rate (ORR) [ Time Frame: After 84 days (3 courses) of treatment ]Will be defined as complete remission (CR), partial remission (PR), or clinical improvement (CI) after 3 courses of treatment according to International Working Group (IWG) consensus criteria for myelofibrosis. The Optimum two-stage design proposed by Simon will be implemented. ORR will be estimated along with the Bayesian 95% credible interval.
- Incidence of grade 3-4 clinically relevant non-hematologic toxicity or a serious adverse event that is at least possibly drug related [ Time Frame: Up to 30 days post-treatment ]Will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Safety data will be summarized by category, severity and frequency. The proportion of patients with adverse events will be estimated, along with the Bayesian 95% credible interval.
- Duration of response [ Time Frame: Date at which the subject's objective status is first noted to the date of progression (no longer meeting criteria for any type of response), assessed up to 30 days post-treatment ]The distribution for duration of response will be estimated by Kaplan-Meier curves.
- Time to response [ Time Frame: Time from study registration to the first date at which the subject's objective status was classified as a response, assessed up to 30 days post-treatment ]The distribution for time to response will be estimated by Kaplan-Meier curves.
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): NCT02098161
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Naveen Pemmaraju||M.D. Anderson Cancer Center|