E1912: A Randomized Phase III Study of Ibrutinib (PCI-32736)-Based Therapy vs Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL)
I. To evaluate the ability of Ibrutinib-based induction therapy to prolong progression free survival (PFS) compared to standard fludarabine phosphate, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy for younger patients with chronic lymphocytic leukemia (CLL).
I. Evaluate overall survival (OS) of patients based on treatment arm. II. Monitor and assess toxicity of treatment with Ibrutinib-based induction relative to standard FCR chemotherapy.
III. To compare quality of life (QOL) in CLL patients during the first 6 months of treatment among patients receiving Ibrutinib-based induction therapy relative to standard FCR chemoimmunotherapy.
IV. To compare QOL over the long-term in CLL patients receiving continuous therapy using Ibrutinib to that of CLL patients who completed FCR therapy.
V. Determine the effect of pretreatment clinical and biological characteristics (e.g. disease stage, immunoglobulin heavy chain variable region gene [IGHV] mutation status, fluorescent in situ hybridization [FISH]) on clinical outcomes (e.g. complete response, PFS) of the different arms.
VI. Determine if the minimal residual disease (MRD) status as assessed by flow cytometry at different time points during and after treatment is an effective surrogate marker for prolonged PFS and overall survival.
VII. Compare the genetic abnormalities and dynamics of intra-clonal architecture of CLL patients before and after treatment with chemoimmunotherapy (CIT) and non-CIT approaches and explore relationships with treatment resistance.
VIII. Explore the effects of FCR and Ibrutinib-based therapy on T-cell immune function.
IX. Conduct confirmatory validation genotyping of single nucleotide polymorphisms (SNPs) associated with the efficacy and toxicity of fludarabine-based therapy as in a prior Eastern Cooperative Oncology Group (ECOG) genome-wide association study (GWAS) analysis in the E2997 trial.
X. Evaluate the ability of prognostic model that incorporates clinical and biologic characters to predict a response to therapy and clinical outcome (PFS, OS).
XI. Evaluate signaling networks downstream of the B-cell receptor in patients receiving Ibrutinib-based therapy.
XII. Collect relapse samples to study mechanisms of resistance to both FCR and Ibrutinib-based therapy.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
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