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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01711632
Recruitment Status : Active, not recruiting
First Posted : October 22, 2012
Last Update Posted : September 19, 2017
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Hairy Cell Leukemia Drug: Vemurafenib Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : October 2012
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia
Drug Information available for: Vemurafenib
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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 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™

Outcome Measures

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Toxicity (safety and tolerability) [ Time Frame: 2 years ]
    Toxicity will be graded and recorded using the NCI Common Toxicology Criteria version 4.0.

  2. 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.

  3. 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.

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • ≥ 18 years of age
  • Histologically confirmed classical HCL with one of the following:
  • Intolerance to purine analogs or considered to be poor candidates for purine analog-based therapy
  • 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

Information from the National Library of Medicine

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): NCT01711632

United States, California
Scripps Clinic
La Jolla, California, United States, 92037
United States, Illinois
Northwestern University
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
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Northwestern University
Ohio State University
Dana-Farber Cancer Institute
Scripps Clinic
Northwell Health
Principal Investigator: Jae H. Park, MD Memorial Sloan Kettering Cancer Center
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01711632     History of Changes
Other Study ID Numbers: 12-200
First Posted: October 22, 2012    Key Record Dates
Last Update Posted: September 19, 2017
Last Verified: September 2017

Keywords provided by Memorial Sloan Kettering Cancer Center:
BRAF Inhibitor

Additional relevant MeSH terms:
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action