Combining Selinexor with R-CHOP for High-risk Diffuse Large B-Cell Lymphoma

Frontline Selinexor(ATG-010) Plus R-CHOP Therapy for High-risk GCB-subtype Diffuse Large B-Cell Lymphoma

This study is testing if adding Selinexor to the standard R-CHOP treatment can help people newly diagnosed with high-risk diffuse large B-cell lymphoma do better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, Rituximab, cyclophosphamide, doxorubicin, prednisone
• Locations: 6 sites (Guangzhou, Guangdong and 5 other locations)
• Trial ID: NCT05422066 on ClinicalTrials.gov

What this trial studies

This phase II, multicenter, single-arm, open-label study investigates the efficacy and safety of Selinexor in combination with the standard R-CHOP regimen for patients newly diagnosed with high-risk germinal center B-cell subtype diffuse large B-cell lymphoma (DLBCL). Approximately 35 patients will receive 6 cycles of R-CHOP along with a fixed weekly dose of Selinexor. Disease assessments will be conducted using PET-CT or PET-MRI scans at specified intervals to monitor treatment response. The study aims to evaluate whether this combination can improve outcomes for patients with a high International Prognostic Index score.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with newly diagnosed high-risk GCB-subtype DLBCL and an IPI score of 3-5.

Not a fit: Patients with prior chemotherapy or radiotherapy for DLBCL or those with an ECOG performance status greater than 2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with high-risk DLBCL, potentially improving survival rates.

How similar studies have performed: While the combination of Selinexor with standard therapies is being explored, this specific approach in high-risk GCB-subtype DLBCL is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

  1. Willing and able to written informed consent (ICF) .
  2. Age ≥ 18 years and ≤ 75 years.
  3. Histologically confirmed Diffuse Large B-Cell Lymphoma of the germinal center B-cell(DLBCL) subtype by Hans.
  4. Patients no prior chemotherapy or radiotherapy for DLBCL, with the exception of no more than 5 days of treatment with glucocorticoids for symptom control.
  5. International Prognostic Index score of 3-5.
  6. Computed Tomography(CT)/Positron emission tomography (PET) positive measurable disease per the Lugano Classification 2014, having at least 1 node with longest diameter (LDi) greater than \> 1.5cm or 1 extranodal lesion with LDi \>1 cm.
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
  8. Adequate bone marrow function at Screening(Except for underlying diseases, such as secondary hypersplenism due to bone marrow invasion or splenic invasion identified by the investigator).

     1. Absolute neutrophil count (ANC)≥1.5×109/L;
     2. Platelet count (PLT) ≥100×109/L(no platelet transfusion within 14 days prior to C1D1), or PLT≥ 75×109/L if due to lymphoma with bone marrow involvement.
     3. Hemoglobin (HB)≥85g/L(no red blood cell transfusion within 14 days prior to C1D1).
  9. Adequate hepatic and renal function:

     1. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤2.0 x upper limit of normal (ULN), or AST and ALT≤5.0 x ULN(if due to lymphoma involvement),
     2. Serum total bilirubin ≤2×ULN, or Serum total bilirubin ≤5×ULN if due to Gilbert syndrome or lymphoma involvement.
     3. Estimated creatinine clearance ≥ 30 mL/min (calculated using the formula of Cockroft-Gault).
  10. Participants of childearing potential must agree to use highly effective methods of contraception during the duration of the study and following the last dose of study treatment, female and male participants should continue contraception for 14 and 11 months, respectively.

      1. Female participants of childbearing potential must have a negative serum pregnancy test at screening(Non-Childbearing potential: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy).
      2. Male participants must agree to avoid sperm donation during the duration of the study and 14 months following the last dose of study treatment.

Exclusion Criteria:

* Inclusion/Exclusion Criteria:

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

1. Willing and able to written informed consent (ICF) .
2. Age ≥ 18 years and ≤ 75 years.
3. Histologically confirmed Diffuse Large B-Cell Lymphoma of the germinal center B-cell(DLBCL) subtype by Hans.
4. Patients no prior chemotherapy or radiotherapy for DLBCL, with the exception of no more than 5 days of treatment with glucocorticoids for symptom control.
5. International Prognostic Index score of 3-5.
6. Computed Tomography(CT)/Positron emission tomography (PET) positive measurable disease per the Lugano Classification 2014, having at least 1 node with longest diameter (LDi) greater than \> 1.5cm or 1 extranodal lesion with LDi \>1 cm.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
8. Adequate bone marrow function at Screening(Except for underlying diseases, such as secondary hypersplenism due to bone marrow invasion or splenic invasion identified by the investigator).

   1. Absolute neutrophil count (ANC)≥1.5×109/L;
   2. Platelet count (PLT) ≥100×109/L(no platelet transfusion within 14 days prior to C1D1), or PLT≥ 75×109/L if due to lymphoma with bone marrow involvement.
   3. Hemoglobin (HB)≥85g/L(no red blood cell transfusion within 14 days prior to C1D1).
9. Adequate hepatic and renal function:

   1. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤2.0 x upper limit of normal (ULN), or AST and ALT≤5.0 x ULN(if due to lymphoma involvement),
   2. Serum total bilirubin ≤2×ULN, or Serum total bilirubin ≤5×ULN if due to Gilbert syndrome or lymphoma involvement.
   3. Estimated creatinine clearance ≥ 30 mL/min (calculated using the formula of Cockroft-Gault).
10. Participants of childearing potential must agree to use highly effective methods of contraception during the duration of the study and following the last dose of study treatment, female and male participants should continue contraception for 14 and 11 months, respectively.

    1. Female participants of childbearing potential must have a negative serum pregnancy test at screening(Non-Childbearing potential: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy).
    2. Male participants must agree to avoid sperm donation during the duration of the study and 14 months following the last dose of study treatment.

Exclusion Criteria:

Patients who meet any of the following criteria will not be enrolled:

1. DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma; composite lymphoma (Hodgkin lymphoma + NHL); Gray zone lymphoma; DLBCL transformed from Chronic Lymphocytic Leukemia (Richter Syndrome); Primary mediastinal large B-cell lymphoma (PMBCL); T-cell rich large B-cell lymphoma.
2. Known active central nervous system lymphoma or meningeal involvement at screening. Participants with a history of CNS disease treated into remission may be enrolled. The DLBCL of Testis involvement or more than two extranodal involvement.
3. Previous treatment with selinexor or other XPO1 inhibitors.
4. Contraindication to any drug contained in these regimen.
5. Major surgery \<14 days of C1D1, Except for disease diagnosis.
6. Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participant's safety, or able to comply with the study procedures.
7. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
8. Subjects with known active Hepatitis B (HB) infection, active Hepatitis C (HCV) infection or Human Immunodeficiency Virus (HIV) positivity. Participants with active hepatitis B Virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 international units per milliliter (IU/mL); participants with untreated hepatitis C Virus (HCV) are eligible if viral load is negative per institutional standard; participants with human immunodeficiency virus (HIV) are eligible if cluster of differentiation 4 (CD4+) T-cell counts ≥350 cells per microliter (cells/μL), viral load is negative and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
9. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
10. Breastfeeding women or pregnant women.
11. In the opinion of the Investigator, participants who are below their ideal body weight and would be unduly impacted by changes in their weight.
12. Life expectancy of less than 6 months.

Where this trial is running

Guangzhou, Guangdong and 5 other locations

• Department of Medical Oncology, Sun Yat-Sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• Hubei Cancer Hospital — Wuhan, Hubei, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• The Affiliated People's Hospital of Ningbo University — Ningbo, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Zhiming Li, Ph.D — Sun Yat-sen University
• Study coordinator: Zhiming Li, Ph.D

Conditions DLBCL Germinal Center B-Cell Type; Selinexor; Xpovio; Newly Diagnosed; DLBCL; IPI 3-5