Clinical Trial: BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II Study of the BRAF Inhibitor, Vemurafenib, in Patients With Relapsed or Refractory Hairy Cell Leukemia

Brief Summary: 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.

Detailed Summary:
Sponsor: Memorial Sloan Kettering Cancer Center

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: Memorial Sloan Kettering Cancer Center

Dates:
Date Received: October 17, 2012
Date Started: October 2012
Date Completion: October 2018
Last Updated: March 16, 2017
Last Verified: March 2017