This phase Ib/II trial is aimed at studying the combination of a drug named Selinexor (selective inhibitor of nuclear export) in combination with standard therapy for B cell Non-Hodgkin's lymphoma called R-CHOP. The investigators will establish maximum tolerated dose of Selinexor in combination with RCHOP and also study the efficacy of this combination for therapy of B cell Non-Hodgkin's lymphoma. Giving Selinexor plus chemotherapy may work better in treating patients with B cell non-Hodgkin lymphoma.
The study will be done in two phases namely phase 1B and phase 2. In the phase 1B component the investigators intend to enroll patients in a 3+3 dose escalation design. Newly diagnosed indolent and diffuse large cell lymphomas as well as relapsed/refractory indolent B cell lymphomas are eligible for enrollment in the phase 1 component. The primary end-point for this component would be to establish the recommended phase 2 dose (RP2D) for Selinexor in combination with standard dose RCHOP chemotherapy. In the phase 2 part of the study the investigators will use recommended phase 2 dose of Selinexor plus standard dose RCHOP combination to treat newly diagnosed DLBCL patients with the primary end-point being 2 year Progression free survival. Maintenance Phase: Patients with Follicular Lymphoma and Diffuse Large B cell lymphoma able to achieve PR or better at the end of therapy scan will be put on maintenance Selinexor for a total of one year. The dose of Selinexor in the maintenance phase would be similar to the last dose used for that particular patient in the treatment phase 1 or 2.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Given PO
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Maximum tolerated dose of selinexor in combination with RCHOP chemotherapy defined as =< 1/6 patients experience a dose limiting toxicity (Phase Ib)
Toxicity grading in both phase 1b and phase 2 parts will be done based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 guidelines. Toxicity data will be collected at least weekly during the course of treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
Time frame: Up to 21 days
Progression-free survival (PFS) for patients with newly diagnosed DLBCL treated with RCHOP-selinexor combination (Phase II)
PFS will be described with Kaplan-Meier curves and estimated medians with 95% confidence intervals.
Time frame: From baseline to disease progression or death from any cause, assessed up to 2 years
CR of patients with newly DLBCL treated with selinexor and RCHOP
Response rates will be estimated as proportions with 95% Wilson confidence intervals.
Time frame: Up to 2 years
PR of patients with newly diagnosed DLBCL treated with selinexor and RCHOP
Response rates will be estimated as proportions with 95% Wilson confidence intervals.
Time frame: Up to 2 years
SD of patients with newly diagnosed DLBCL treated with selinexor and RCHOP
Response rates will be estimated as proportions with 95% Wilson confidence intervals.
Time frame: Up to 2 years
ORR (CR and PR) of patients with newly diagnosed DLBCL treated with selinexor and RCHOP
Response rates will be estimated as proportions with 95% Wilson confidence intervals.
Time frame: Up to 2 years
OS of patients with newly diagnosed DLBCL treated with RCHOP-selinexor combination
OS will be described with Kaplan-Meier curves and estimated medians with 95% confidence intervals.
Time frame: Baseline to date of death, assessed up to 2 years
Change in CRM1/XPO-1 activity expression assessed in tissue by polymerase chain reaction (PCR)
Difference in the CRM-1 activity by PCR in the tumor tissue and peripheral blood samples obtained at baseline and at 48-72 hours after cycle 1 day1 of therapy.
Time frame: Baseline and at 48-72 hours after cycle 1 day 1
Change in CRM1/XPO-1 activity expression assessed in tissue by immunohistochemistry (IHC)
Difference in the CRM-1 activity by IHC in the tumor tissue and peripheral blood samples obtained at baseline and at 48-72 hours after cycle 1 day1 of therapy.
Time frame: Baseline and at 48-72 hours after cycle 1 day 1
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