Selinexor Plus R-CHOP in High-risk GCB-subtype Diffuse Large B-Cell Lymphoma

Launched by LI ZHIMING · Jun 13, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with a type of cancer called Diffuse Large B-Cell Lymphoma (DLBCL), specifically the germinal center B-cell subtype. Researchers are testing a medication called Selinexor combined with the standard treatment known as R-CHOP. This trial aims to find out how safe and effective this combination is for patients who are newly diagnosed and considered high-risk, based on specific scoring criteria.

To participate in this trial, patients should be between 18 and 75 years old, have a confirmed diagnosis of the germinal center subtype of DLBCL, and have not received prior chemotherapy or radiation for their lymphoma. Patients will undergo up to six cycles of treatment over about 18 months. Throughout the study, they will be monitored for their health and response to treatment. It's important to note that this trial is currently recruiting participants, and those interested should discuss it with their doctor to see if they qualify.

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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.