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

NCT01711632 | Completed Phase 2 Results

• 1 other identifier: 12-200
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

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.

Conditions

Hairy Cell Leukemia

Keywords

VEMURAFENIB; BRAF Inhibitor; 12-200; Zelboraf™

Outcome Measures

Primary Outcomes (1)

• Efficacy of Vemurafenib

  as assessed by overall response rates after three months of treatment in patients with relapsed or refractory HCL. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  3 months

Secondary Outcomes (3)

• Toxicity (Safety and Tolerability)

  2 years

• To Assess the Pharmacodynamics Change From Baseline

  2 years

• Evaluate Biomarkers of Resistance

  2 years

Study Arms (1)

Vemurafenib

EXPERIMENTAL

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

Interventions

Vemurafenib DRUG

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.

Also known as: Zelboraf™

Vemurafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Northwestern University: collaborator
• Ohio State University: collaborator
• Dana-Farber Cancer Institute: collaborator
• Scripps Clinic: collaborator
• Northwell Health: collaborator

Study Sites (5)

Scripps Clinic

La Jolla, California, 92037, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (2)

• Handa S, Lee JO, Derkach A, Stone RM, Saven A, Altman JK, Grever MR, Rai KR, Shukla M, Vemuri S, Montoya S, Taylor J, Abdel-Wahab O, Tallman MS, Park JH. Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy. Blood. 2022 Dec 22;140(25):2663-2671. doi: 10.1182/blood.2022016183.

  PMID: 35930750 DERIVED

• Tiacci E, Park JH, De Carolis L, Chung SS, Broccoli A, Scott S, Zaja F, Devlin S, Pulsoni A, Chung YR, Cimminiello M, Kim E, Rossi D, Stone RM, Motta G, Saven A, Varettoni M, Altman JK, Anastasia A, Grever MR, Ambrosetti A, Rai KR, Fraticelli V, Lacouture ME, Carella AM, Levine RL, Leoni P, Rambaldi A, Falzetti F, Ascani S, Capponi M, Martelli MP, Park CY, Pileri SA, Rosen N, Foa R, Berger MF, Zinzani PL, Abdel-Wahab O, Falini B, Tallman MS. Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia. N Engl J Med. 2015 Oct 29;373(18):1733-47. doi: 10.1056/NEJMoa1506583. Epub 2015 Sep 9.

  PMID: 26352686 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia, Hairy Cell

Interventions

Vemurafenib

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jae Park, MD
• Organization: Memorial Sloan Kettering Cancer Center

parkj6@mskcc.org

646-608-3743

Study Officials

• Jae H. Park, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2012
• First Posted: October 22, 2012
• Study Start: October 1, 2012
• Primary Completion: August 16, 2024
• Study Completion: August 16, 2024
• Last Updated: October 20, 2025
• Results First Posted: October 20, 2025

Record last verified: 2024-08

Locations

US (5)