SHS_492328 PAGJ CCRS 16050
Open-Label, Phase 2 Study to Evaluate the Efficacy and Safety of CUDC-907 With and Without Rituximab in Patients With Relapsed/Refractory MYC-Altered Diffuse Large B-Cell Lymphoma
This is a Phase 2, open-label, multicenter trial designed to evaluate the efficacy and safety of CUDC-907 monotherapy and R-907 (rituximab in combination with CUDC-907) in subjects 18 years and older with Relapsed/Refractory (RR) MYC-altered Diffuse Large B-Cell Lymphoma (DLBCL).
•Age ≥ 18 years.
•At least two but no more than 4 prior lines of therapy for the treatment of DLBCL and ineligible for (or failed) autologous or allogeneic stem cell transplant (salvage therapy, conditioning therapy and maintenance with transplant will be considered one prior treatment).
•Histopathologically confirmed diagnosis of RR DLBCL. • Diagnosis of follicular lymphoma transformed to DLBCL (aka transformed DLBCL) is allowed. Other B-cell lymphomas including DLBCL unclassified and Burkitt's lymphoma are not eligible.
•Histopathologically confirmed MYC-altered disease by archival tumor samples (collected within 1 year of study entry and/or within 1 line of prior therapy, whichever is closer to the time of study entry) or fresh tumor samples by one of the following: (1) Local or central laboratory (if local testing is not available) fluorescence in situ hybridization (FISH) results of MYC translocation, or (2) Local or central laboratory (if local testing is not available) immunohistochemical (IHC) results with expression of MYC in ≥ 40% of tumor cells, and/or MYC gene copy number gain by FISH.
•Confirmed availability of viable tissue (defined as archival tissue collected within 1 year of study entry and/or within 1 line of prior therapy, whichever is closer to the time of study entry, or fresh tumor samples) for central laboratory FISH and IHC testing and review prior to study dosing.
•Known primary mediastinal, ocular, epidural, testicular or breast DLBCL.
•Known lymphomatous involvement of the central nervous system (CNS) unless deemed clear of malignant involvement by cytologic examination of cerebrospinal fluid. Subjects with known bone marrow involvement will require prior chemoprophylaxis per local standard to prevent CNS relapse.
•Known allergy or hypersensitivity to phosphatidylinositol 3 kinase (PI3K) inhibitors or any component of the formulations used in this study. Prior treatment with an histone deacetylase (HDAC) inhibitor is not allowed (whereas prior treatment with a PI3K inhibitor is allowed).
•Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine analogues) within 2 weeks of study entry.
•Radiotherapy delivered to target lesions that will be followed on the study (note: prior sites of radiation will be recorded).
•Treatment with experimental therapy within 5 terminal half-lives (t1/2) or 4 weeks prior to enrollment, whichever is longer.
•Current or planned glucocorticoid therapy, with the following exceptions: Glucocorticoids to reduce the potential for infusion reactions to rituximab are allowed per institutional guidelines. Doses ≤ 1 mg/kg/day prednisolone or equivalent glucocorticoid and inhalational therapies for conditions such as mild chronic obstructive pulmonary disease (COPD) and asthma are allowed. Replacement dosing of steroids (defined as < 30 mg/day hydrocortisone or the equivalent) is allowed, provided that the steroid dose has been stable or tapering for at least 14 days prior to the first dose of CUDC-907.
John Pagel, M.D.