A Single-arm, Multi-center, Phase Ib/II Study of Selinexor in Combination With R-CHOP Followed by Selinexor Maintenance for Untreated EBV-positive DLBCL Patients (Xplore Trial)
Overview
- Phase
- Phase 1
- Intervention
- Selinexor
- Conditions
- EBV-Positive Diffuse Large B-Cell Lymphoma, Nos
- Sponsor
- Sun Yat-sen University
- Enrollment
- 54
- Locations
- 2
- Primary Endpoint
- Complete response rate (CRR)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Qingqing Cai
chief physician
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Subjects fully understand and voluntarily participate in this study and sign informed consent
- •Age ≥18, ≤70 years, no gender limitation.
- •Histologically confirmed diagnosis of EBV-positive diffuse large B-cell lymphoma (DLBCL) (more than 50% of tumor cells are positive with EBV encoded small RNAs (EBERs) in situ hybridization were considered EBERs positive).
- •Untreated patients, except for the short-time use of prednisone for controlling tumor-induced symptoms (no more than 30mg/d (or other equivalent amounts of other glucocorticoids), no more than 7 days).
- •There must be at least one measurable or evaluable lesion that meets the evaluation criteria for Lugano 2014 lymphoma: measurable lesion: Positron emission tomography/computed tomography (PET/CT) or CT and/or MRI, intranodal lesions with long diameter \>1.5cm, and short diameter \>1.0cm, or extranodal lesions with long diameter \> 1.0 cm.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-
- •Expected survival ≥ 3 months.
- •Adequate function of bone marrow:
- •White blood cell ≥3.0×10E9/L, absolute neutrophil count ≥1.5×10E9/L Platelet ≥100×10E9/L (Bone marrow invasive patient≥75×109/L) Hemoglobin≥ 90g/L No granulocyte growth factor, platelet, or red blood cell transfusions were received within 14 days prior to examination.
- •Adequate function of the liver and renal:
Exclusion Criteria
- •EBV-positive DLBCL combined with other types of lymphoma. Transformed DLBCL.
- •EBV-positive DLBCL with central nervous system invasion.
- •The patients had previously received XPO1 inhibitors, such as selinexor and so on.
- •The patients have contraindications to any drug in the combined treatment.
- •The major surgery is performed within 4 weeks before enrollment, except for diagnosis.
- •There are any life-threatening diseases, medical conditions or organ system dysfunction that the investigator believes may affect the safety or compliance of patients.
- •Heart function and disease meet one of the following conditions:
- •Heart failure with the classification of New York Heart Association heart function of grade II;
- •A history of unstable angina pectoris;
- •A history of myocardial infarction within the past 1 years;
Arms & Interventions
Selinexor in Combination With R-CHOP
Patients with untreated EBV-positive diffuse large B-cell lymphoma will receive sequentially higher doses of selinexor in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle).The initial dose of selinexor is 40mg qw po. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
Intervention: Selinexor
Selinexor in Combination With R-CHOP
Patients with untreated EBV-positive diffuse large B-cell lymphoma will receive sequentially higher doses of selinexor in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle).The initial dose of selinexor is 40mg qw po. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
Intervention: R-CHOP Protocol
Outcomes
Primary Outcomes
Complete response rate (CRR)
Time Frame: Up to 24 weeks.
To investigate the preliminary antitumor efficacy
Maximum tolerated dose (MTD)
Time Frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
To identify the MDT
Recommended Phase II Dose (RP2D)
Time Frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
To identify the RP2D
Secondary Outcomes
- Disease-free survival (DFS)(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)(Up to 24 weeks.)
- Progression-free survival (PFS)(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)(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(Through study completion, an average of 2 years.)