A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia

Inclusion Criteria:

* Patients must be \>/= 18 years of age
* Histologically confirmed classical HCL by the enrolling institution
* Has not received any prior therapy for the disease
* 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
  * 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 (QT 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 with 7 days of commencement of treatment in women of childbearing potential

Exclusion Criteria:

* Have had previous treatment for HCL, including purine analogs, rituximab, and other investigational agents. Previous treatment with transfusions and other supportive care such as G-CSF and erythropoietin are allowed.
* Known hypersensitivity to any of the study drugs
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
* Patients with uncorrectable electrolyte abnormalities with potassium (K) \>ULN (upper limit of normal).
* Patients with any active and uncontrolled infections (such as bacterial, fungal, and new or reactivated viral infections)
* Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody.

  * Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation.
  * Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing.
* Known infection with HIV or human T-cell leukemia virus 1 (HTLV-1)
* Invasive malignancy that require active systemic chemotherapy or biologics that may cause significant drug-drug interaction with either vemurafenib or obinutuzumab
* Malabsorption syndrome or other condition that precludes enteral route of administration
* Patients with HCL variant (as defined by absence of expression of CD25)
* Pregnant or lactating, or intending to become pregnant during the study