This phase II trial studies how well vemurafenib and obinutuzumab work in treating patients with previously untreated classical hairy cell leukemia. Vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Obinutuzumab is a drug that targets a protein called CD20, which is found on the surface of B cells, the white blood cells that are affected by hairy cell leukemia. When obinutuzumab attaches to CD20, it directly destroys the B cells and makes them more visible to the immune system, which then helps them attack and destroy the cancerous B cells. Giving vemurafenib and obinutuzumab may help shrink the cancer in patients with previously untreated hairy cell leukemia.
Additional locations may be listed on ClinicalTrials.gov for NCT03410875.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To determine the efficacy of vemurafenib in combination with obinutuzumab as assessed by complete response (CR) rates.
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of vemurafenib plus obinutuzumab in patients with previously untreated hairy cell leukemia (HCL).
II. To assess the efficacy of vemurafenib plus obinutuzumab based on duration of response and kinetics of minimal residual disease (MRD) response assessed by immunohistochemistry.
III. To determine the progression-free and overall survival of HCL patients treated with vemurafenib plus obinutuzumab.
IV. To assess the pharmacodynamics of vemurafenib and obinutuzumab via measurement of BRAF downstream targets (MEK, phosphorylated [p]-MEK, ERK, p-ERK) from the peripheral blood and/or bone marrow aspirate samples and by measurement of BRAFV600E allele burden by digital polymerase chain reaction (PCR).
V. To evaluate the potential mechanisms of resistance by assessing secondary BRAF mutations, signaling on the entire MAPK, PI3K and JAK-STAT pathways, and reactivation of MAPK pathways.
OUTLINE:
Patients receive vemurafenib orally (PO) twice daily (BID) on days 1-28 of all cycles. Beginning cycle 2, patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 2 and on day 1 of cycle 3 and 4. Treatment repeats every 28 days for up to 4 cycles of vemurafenib and for up to 3 cycles of obinutuzumab in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 weeks and every 2-3 months thereafter for 1 year.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorJae Park
