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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Northwestern University
Ohio State University
Dana-Farber Cancer Institute
Scripps Clinic
North Shore Long Island Jewish Health System
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01711632
First received: October 17, 2012
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Hairy Cell Leukemia
Drug: Vemurafenib
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 36
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)
Arms Assigned Interventions
Experimental: Vemurafenib
Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days).
Drug: Vemurafenib
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 18 years of age
  • Histologically confirmed classical HCL with one of the following:
  • Intolerance to purine analogs
  • Failure to achieve any response (CR or PR) to the initial purine analog-based therapy
  • Relapse ≤ 2 years of purine analog-based therapy
  • ≥ 2 relapses Histologic confirmation of diagnosis will be performed at MSKCC or a participating site.
  • Patients who meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K
  • ECOG performance status of 0-2
  • Acceptable pre-study organ function during screening as defined as: Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN, and serum creatinine ≤ 1.5x ULN
  • Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett's formula) of < 480 msec.
  • For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of vemurafenib
  • For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of vemurafenib
  • Negative serum pregnancy test within 7 days of commencement of treatment in premenopausal women.
  • Agreement not to donate blood or blood products during the study and for at least 6 months after discontinuation of vemurafenib; for male partners, agreement not to donate sperm during the study and for at least 6 months after discontinuation of vemurafenib
  • Ability to understand and willingness to sign a written informed consent document.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

  • Pregnant or breast-feeding
  • Have had chemotherapy (including purine analogs, rituximab, and other investigational agents) within six weeks prior to entering the study
  • Major surgery within 4 weeks prior to entering the study
  • Invasive malignancy within the past 2 years prior to first study drug administration, except for adequately treated (with curative intent) basal or squamous cell carcinoma, melanoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other cancers from which the patient has been disease-free for at least 2 years
  • Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug
  • Prior treatment with MEK or BRAF inhibitors
  • Active HIV, hepatitis B and hepatitis C
  • Patients with HCL variant (as defined by absence of expression of CD25 or absence of BRAF V600E mutation)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01711632

Contacts
Contact: Jae H Park, MD 212 639-4048
Contact: Martin S. Tallman, MD 212 639-3842

Locations
United States, California
Scripps Clinic Recruiting
La Jolla, California, United States, 92037
Contact: Alan Saven, MD         
Principal Investigator: Alan Saven, MD         
United States, Illinois
Northwestern University Recruiting
Evanston, Illinois, United States, 60208
Contact: Jessica Altman, MD         
Principal Investigator: Jessica Altman, 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         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Michael Grever, MD         
Principal Investigator: Michael Grever, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Northwestern University
Ohio State University
Dana-Farber Cancer Institute
Scripps Clinic
North Shore Long Island Jewish Health System
Investigators
Principal Investigator: Jae H. Park, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01711632     History of Changes
Other Study ID Numbers: 12-200
Study First Received: October 17, 2012
Last Updated: July 17, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
VEMURAFENIB (PLX4032 or R05185426)
BRAF Inhibitor
12-200

Additional relevant MeSH terms:
Leukemia
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 15, 2014