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

This is an interventional treatment trial for Hairy Cell Leukemia focused on measuring Leukemia, Hairy Cell Leukemia, BRAF, vemurafenib, obinutuzumab, Memorial Sloan Kettering Cancer Center, 17-513 Read More

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