This is a prospective, single-arm, multi-center, phase Ib/II clinical trial to evaluate the safety, tolerability, and efficacy of selinexor in combination with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) followed by selinexor maintenance for untreated EBV-positive diffuse large B-cell lymphoma (DLBCL) patients.
This is a prospective, single-arm, multi-center, phase Ib/II clinical trial to explore the maximum tolerated dose (MTD) of selinexor when combined with R-CHOP regimen for untreated EBV-positive DLBCL patients. Phase Ib study: Selinexor will be given orally at two different doses (40mg qw, and 60mg qw ) and combined with the R-CHOP regimen from the second cycle based on the "3+3" principle. In the induction therapy period, 6 cycles of R-CHOP regimen and 2 cycles of rituximab in combination with selinexor are planned. The dose limited toxicity (DLT) will be evaluated after the first cycle of selinexor in combination with R-CHOP. Phase II study: The phase II study of selinexor at recommended phase II dose (RP2D) dose level combined with R-CHOP regimen was conducted to explore the efficacy and safety of the combined regimen. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Selinexor: 40mg qw po, and 60mg qw po (phase Ib); RP2D (II study); Selinexor is added from the second cycle of R-CHOP regimen.
Rituximab: 375mg/m2 iv.drip D1; Cyclophosphamide: 750mg/m2 iv.drip D1; Doxorubicin: 50mg/m2 iv.drip D1; Vincristine: 1.4g/m2 iv D1; Prednisone: 100mg po D1-5;
Sun Yat-sen Universitiy Cancer Center
Guangzhou, Guangdong, China
RECRUITINGFudan University Shanghai Cancer Center
Shanghai, China
RECRUITINGMaximum tolerated dose (MTD)
To identify the MDT
Time frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
Recommended Phase II Dose (RP2D)
To identify the RP2D
Time frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
Complete response rate (CRR)
To investigate the preliminary antitumor efficacy
Time frame: Up to 24 weeks.
Disease-free survival (DFS)
To investigate the preliminary antitumor efficacy
Time frame: From date of the first complete response until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Objective response rate (ORR)
To investigate the preliminary antitumor efficacy
Time frame: Up to 24 weeks.
Progression-free survival (PFS)
To investigate the preliminary antitumor efficacy
Time frame: From date of the first injection until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Overall survival (OS)
To investigate the preliminary antitumor efficacy
Time frame: From date of the first injection until the date of death from ant cause, assessed up to 24 months
Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0
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To identify the incidence of AE and SAE
Time frame: Through study completion, an average of 2 years.