BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia
The purpose of this study is to find out what effects, good and/or bad, treatment with vemurafenib (also known as Zelboraf™) has on the patient and on leukemia. Specifically, the researchers want to know how well vemurafenib eliminates leukemia from the blood.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of the BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia|
- efficacy of vemurafenib [ Time Frame: 3 months ] [ Designated as safety issue: No ]as assessed by overall response rates after three months of treatment in patients with relapsed or refractory HCL.
- Toxicity (safety and tolerability) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Toxicity will be graded and recorded using the NCI Common Toxicology Criteria version 4.0.
- To assess the pharmacodynamics [ Time Frame: 2 years ] [ Designated as safety issue: No ]Peripheral blood and/or bone marrow aspirate samples from pretreatment and post-treatment at specified time points will be assessed by Western Blot or by phospho-flow for the downstream targets of BRAF (MEK, pMEK, ERK, pERK) to assess the ontarget effect of the Vemurafenib.
- evaluate biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]Reactivation of MAPK pathways: Increased expression of the other RAF isoforms CRAF and ARAF), and MAPK (MAPK8 or COT) will be analyzed by Western Blot and/or real-time PCR39,40. Secondary BRAF mutations (all 18 BRAF exons) and RAS mutations40 will be analyzed by bidirectional Sanger sequencing and by Raindance multiplex PCR and Illumina next generation sequencing, respectively. Activation of RTKs (i.e. PDGFRβ and IGF-IR) will be assessed by Western Blot. Cell Biosciences NanoPro 1000 technology will be used to examine quantitative signaling on the entire MAPK, PI3K and JAK-STAT pathways41.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||October 2015|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
Patients will receive vemurafenib at a dose of 960mg orally b.i.d. continuously in cycles of 4 weeks (28 days) as outpatient. A bone marrow aspirate and/or biopsy will be performed after the first cycle. After the completion of the third cycle, a repeat bone marrow aspirate and/or biopsy will be performed for assessment of response and evaluation of MRD. Patients who achieve CR with MRD or PR may be retreated with vemurafenib for up to 3 additional cycles at the treating physician's discretion. Patients who achieve a CR without MRD will be observed, and will be treated with vemurafenib for up to 3 additional cycles at the time of relapse (either hematologic or by MRD). Patients who are re-treated after observation will follow the treatment/evaluation plan of Cycles 1-3, except the Cycle 1 Week 1-3 research bloods and Cycle 2 Day 1research bone marrow biopsy and/or aspirate. Patients who achieve no response after the initial 3 cycles of vemurafenib will be removed from the study.
|Contact: Jae H Park, MD||212 639-4048|
|Contact: Martin S. Tallman, MD||212 639-3842|
|United States, California|
|La Jolla, California, United States, 92037|
|Contact: Alan Saven, MD|
|Principal Investigator: Alan Saven, MD|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Robert Stone, MD|
|Principal Investigator: Robert Stone, MD|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Jae Park, MD 212-639-4048|
|Contact: Martin S. Tallman, MD 212-639-3842|
|Principal Investigator: Jae Park, MD|
|Principal Investigator:||Jae H. Park, MD||Memorial Sloan-Kettering Cancer Center|