Trial Outcomes & Findings for Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas (NCT NCT03220022)

Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas

Will be descriptive and will be reported in tabular format with the appropriate summary statistics (count and percentage). In the dose-finding portion, the number of dose limiting toxicities (DLTs) identified among the DLT-evaluable subjects will be listed and summarized by dose level. The safety variables will be listed and summarized for (1) subjects in the dose-finding portion, (2) subjects in the dose expansion cohort (DEC), and (3) all subjects in the study.

Will be descriptive and will be reported in tabular format with the appropriate summary statistics (count and percentage). In the dose-finding portion, the number of DLTs identified among the DLT-evaluable subjects will be listed and summarized by dose level. The safety variables will be listed and summarized for (1) subjects in the dose-finding portion, (2) subjects in the DEC, and (3) all subjects in the study.

Toxicity data will be presented by type and severity for each dose cohort. Incidence of toxicity related dose reductions and treatment discontinuations will be summarized for each dose group.

The complete response rates and their corresponding 95% confidence intervals will be calculated for participants with AIDS-related lymphomas (ARL) treated with combination ibrutinib and rituximab (R)-dose adjusted (da)-etoposide, prednisone, vincristine sulfate, cyclophosphamide and doxorubicin hydrochloride (EPOCH). Response is currently assessed on the basis of clinical, radiologic, and pathologic (i.e., bone marrow) criteria. Radiologic response will be based on the Lugano Classification. Complete metabolic response with Score 1, 2, or 3 with or without a residual mass on 5PS. Partial metabolic response with Score 4 or 5† with reduced uptake compared with baseline and residual mass(es) of any size. Overall Response (OR) consists of complete response and partial response.

PFS will be estimated using Kaplan Meier method, as well as, their corresponding 95% confidence intervals. Progressive disease requires at least 1 of the following Perpendicular diameters: An individual node/lesion must be abnormal with: longest diameter 1.5 cm and Increase by 50% from perpendicular diameters nadir and an increase in longest diameter or shortest diameter from nadir 0.5 cm for lesions 2 cm 1.0 cm for lesions 2 cm. In the setting of splenomegaly, the splenic length must increase by 50% of the extent of its prior increase beyond baseline (e.g., a 15-cm spleen must increase to 16 cm). If no prior splenomegaly, must increase by at least 2 cm from baseline.

PFS will be estimated using Kaplan Meier method, as well as, their corresponding 95% confidence intervals. Progressive disease requires at least 1 of the following Perpendicular diameters: An individual node/lesion must be abnormal with: longest diameter 1.5 cm and Increase by 50% from perpendicular diameters nadir and an increase in longest diameter or shortest diameter from nadir 0.5 cm for lesions 2 cm 1.0 cm for lesions 2 cm. In the setting of splenomegaly, the splenic length must increase by 50% of the extent of its prior increase beyond baseline (e.g., a 15-cm spleen must increase to 16 cm). If no prior splenomegaly, must increase by at least 2 cm from baseline.

OS will be estimated using Kaplan Meier method, as well as, their corresponding 95% confidence intervals.

OS will be estimated using Kaplan Meier method, as well as, their corresponding 95% confidence intervals.

Responses are tabulated by gene expression profiling (GEP) (germinal center B-cell \[GCB\], activated B-cell \[ABC\], unclassifiable) and immunohistochemistry \[IHC\] (GCB, non-GCB).

Hematologic toxicities will be calculated.

Average number of days will be calculated.

Descriptive statistics will be used to evaluate the changes and will be compared with treatment completion. If there are sufficient data, the binomial test of proportions will be used to test if the long term viral reservoir is either undetectable or below baseline in at least half of the participants.

Descriptive statistics will be used to evaluate the changes and compared with treatment completion. If there are sufficient data, the binomial test of proportions will be used to test if the long term viral reservoir is either undetectable or below baseline in at least half of the participants.

Will be correlated with degree of ITK inhibition and Pearson or Spearman correlation coefficients will be used, as appropriate.

Descriptive statistics will be used.

Descriptive statistics will be used.

Descriptive statistics will be used.

Relevant individual PK parameters will be estimated using non-compartmental or compartmental PK methods with the software WinNonlin. The PK variables will be tabulated and descriptive statistics (e.g., geometric means and coefficients of variation) and compared across dose levels (if applicable) using nonparametric statistical testing techniques. PK parameters (i.e., steady state concentration \[Css\], clearance \[Cl\], and area under the curve \[AUC\]) will be correlated with pharmacodynamics effects using nonparametric statistical testing techniques.

Survival rates (PFS and OS at 1 year and 2 years) are reported by gene expression profiling (GEP) (germinal center B-cell \[GCB\], activated B-cell \[ABC\], unclassifiable) and immunohistochemistry \[IHC\] (GCB, non-GCB).