BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia
|ClinicalTrials.gov Identifier: NCT01711632|
Recruitment Status : Active, not recruiting
First Posted : October 22, 2012
Last Update Posted : February 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hairy Cell Leukemia||Drug: Vemurafenib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of the BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia|
|Actual Study Start Date :||October 2012|
|Estimated Primary Completion Date :||October 2018|
|Estimated Study Completion Date :||October 2018|
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 for research purposes only. 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. Following the third cycle assessments, patients who achieve complete response (CR) with detectable MRD or partial response (PR) may continue with vemurafenib for up to 3 additional cycles at the treating physician's discretion (Cycles 4-6). Patients who achieve CR without MRD will be observed as part of post-treatment followup, and may be re-treated with vemurafenib after relapse (as per below). Patients who achieve no response (NR) after the initial 3 cycles of vemurafenib will be removed from the study. They will be followed every 3 months as part of posttreatment followup for a total of 12 months.
Other Name: Zelboraf™
- efficacy of vemurafenib [ Time Frame: 3 months ]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 ]Toxicity will be graded and recorded using the NCI Common Toxicology Criteria version 4.0.
- To assess the pharmacodynamics [ Time Frame: 2 years ]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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01711632
|United States, California|
|La Jolla, California, United States, 92037|
|United States, Illinois|
|Evanston, Illinois, United States, 60208|
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Ohio|
|Ohio State University|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Jae H. Park, MD||Memorial Sloan Kettering Cancer Center|