There is one clinical trial.
This randomized phase III trial studies rituximab with bendamustine hydrochloride or ibrutinib to see how well they work compared to ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether rituximab with bendamustine hydrochloride may work better than rituximab and ibrutinib or ibrutinib alone in treating chronic lymphocytic leukemia.
To assess whether the Fc fragment of IgG, low affinity IIIa, receptor (CD16a) (FCGR3A) polymorphism (rs396991) is correlated with depth of response (MRD status) to ibrutinib plus rituximab after 6 cycles, with secondary endpoints CR rate, rapidity of response, and progression-free survival (PFS).
Description: Log-rank statistics will be used to compare the PFS distributions of the different treatment arms. Progression is defined as any one of the following: an increase in number of blood lymphocytes by >= 50%, >= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, >= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of hemoglobin [Hb] levels > 2g/dL). The methods of Kaplan and Meier will be used to estimate PFS for the treatment arms. For each of the planned comparisons, will assess the corresponding hazard ratios, and PFS medians along with their 95% confidence intervals.
Measure: Progression free survival (PFS) Time: Time from study entry to the time of documented disease progression or death, assessed up to 10 yearsDescription: The Kaplan-Meier method will be used to estimate OS distributions in this chronic lymphocytic leukemia (CLL) population. OS will be measured from the date of registration to the date of the event (i.e., death) or the date of last follow-up to evaluate that event. Patients who are event-free at their last follow-up evaluation will be censored at that time point.
Measure: Overall survival (OS) Time: From the date of registration to the date of death, assessed up to 10 yearsDescription: The Kaplan-Meier method will be used to estimate the rate of progression free survival at 2 years in this CLL population. Progression is defined as any one of the following: an increase in number of blood lymphocytes by >= 50%, >= 50% increase in the products of at least 2 lymph nodes on 2 consecutive determination 2 weeks apart, >= 50% increase in the size of the liver/spleen, transformation to a more aggressive histology, progression of any cytopenia (i.e. decrease of Hb levels > 2g/dL). Progression free survival time will be the time to either progression or death whichever occurs first.
Measure: Progression Free Survival at 2 years Time: From the date of registration to the date of disease progression, assessed up to 10 yearsDescription: Duration of response is defined for all evaluable patients who have achieved an objective response (i.e., CR, nPR, PR) and will be calculated as the length of time from the date at which the patient's objective status is first noted to be a response to the date that progression or death is documented (if one has occurred) or to the date of last follow-up (for those patients who have not progressed or died). Complete response (CR) requires all of the following : absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Partial response (PR) requires a >= 50% decrease in peripheral lymphocyte count from pre-treatment value, >= 50% reduction in lymphadenopathy, and/or ≥ 50% reduction in splenomegaly/hepatomegaly. Patients who fulfill the criteria of CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR)
Measure: Duration of response (complete response [CR], nodular partial response [nPR], and partial response [PR]) Time: From the date at which the patient's objective status is first noted to be a response to the date that progression or death is documented (if one has occurred) or to the date of last follow-up, assessed up to 10 yearsDescription: Complete response (CR) requires all of the following : absence of lymphadenopathy > 1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Partial response (PR) requires a >= 50% decrease in peripheral lymphocyte count from pre-treatment value, >= 50% reduction in lymphadenopathy, and/or ≥ 50% reduction in splenomegaly/hepatomegaly. Patients who fulfill the criteria of CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). Estimated using the number of patients with the type of response of interest divided by the total number of patients randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for true response rates will be calculated.
Measure: Proportion of patients achieving any response to treatment (overall response rate [ORR] [partial response (PR) + nodular partial response (nPR) + complete response (CR)]) Time: Up to 10 yearsDescription: Complete response (CR) requires all of the following : absence of lymphadenopathy >1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Estimated using the number of patients with the type of response of interest divided by the total number of patients randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for true response rates will be calculated
Measure: Proportion of patients achieving a biopsy-proven complete response (CR) Time: Up to 10 yearsDescription: Complete response (CR) requires all of the following : absence of lymphadenopathy >1.5 cm on physical exam/CT scan, no hepatomegaly or splenomegaly, no clonal B-cells in the blood, Normal CBC, bone marrow aspirate and biopsy must be normocellular for age. Patients who fulfill the criteria of CR with exception of having bone marrow lymphoid CLL nodules will be considered a nodular PR (nPR). Estimated using the number of patients with the type of response of interest divided by the total number of patients randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for true response rates will be calculated
Measure: Complete and nodular partial response (nPR) rate Time: Up to 10 yearsDescription: Estimated using the number of patients who achieve minimal residual disease divided by the total number randomized to that treatment arm. Corresponding exact binomial 95% confidence intervals for MRD rates will be calculated.
Measure: Proportion of patients who attain minimal residual disease (MRD) negative status Time: Up to 10 yearsDescription: Will be assessed.
Measure: Proportion of patients who experience grade 3 or higher non-hematologic toxicities Time: Up to 10 yearsDescription: Assessed using the Older Americans' Resources and Services Multidimensional Functional Assessment Questionnaire, Activities of Daily Living, Medical Outcomes Study physical functioning, Karnofsky performance status rated by a health care professional, Karnofsky performance status rated by the patient, timed "Up and Go", and number of falls in the last six months.
Measure: Geriatric functional status (optional) Time: Up to 10 years