Low Dose Vemurafenib and Rituximab in Hairy Cell Leukemia

Inclusion Criteria:

• ≥ 18 years of age

• Histologically confirmed HCL that are BRAF V600E positive by IHC or NGS

• Patient's must meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K

• Patients can either have (1) not received any prior therapy for the disease or havehad (2) failure to achieve any response to the initial purine analog-based therapyor (3) subsequent relapse after any prior therapy.

• ECOG performance status of 0-2

• Acceptable pre-study organ function during screening not exacerbated by Hairy CellLeukemia. General thresholds should be a total bilirubin ≤ 1.5 times the upper limitof normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN, and serum creatinine ≤ 1.5x ULN

• For women of childbearing potential, agreement to use acceptable methods ofcontraception

• For men with female partners of childbearing potential, agreement to use barriercontraception

• Negative serum pregnancy test within 7 days of commencement of treatment inpremenopausal women.

• Ability to understand and willingness to sign a written informed consent document.

• Willingness and ability to comply with scheduled visits, treatment plans, laboratorytests, and other study procedures.

Exclusion Criteria:

• Pregnant or breast-feeding or intending to become pregnant during the study

• Have had chemotherapy (including purine analogs), rituximab, and otherinvestigational agents within six weeks prior to entering the study. The patientscannot have received BRAF inhibitor therapy within 6 months of entering the study.

• Major surgery within 4 weeks prior to entering the study

• Invasive malignancy within the past 2 years prior to first study drugadministration, except for adequately treated (with curative intent) basal orsquamous cell carcinoma, melanoma, in situ carcinoma of the cervix, in situ ductaladenocarcinoma of the breast, in situ prostate cancer, or limited stage bladdercancer or other cancers from which the patient has been disease-free for at least 2years

• Active HIV, hepatitis B and hepatitis C or any clinically significant history ofliver disease. Hepatitis B prior infection is not a contraindication though willrequire therapy.

• Known hypersensitivity to any of the study drugs

• Patients with HCL that are BRAF V600E mutation negative