Selinexor Combined With R-GDP Regimen for TP53-altered R/R DLBCL

Launched by RUIJIN HOSPITAL · Sep 29, 2023

Keywords

ClinConnect Summary

This clinical trial is testing a new treatment option for patients with a type of blood cancer called B-cell lymphoma, specifically those whose cancer has certain genetic changes (TP53 alterations) and has not responded to previous treatments. The study will explore how well a combination of two treatments—selinexor and a regimen called R-GDP—works in fighting this cancer. It aims to determine both the effectiveness and safety of this combination therapy.

To participate in the trial, individuals must be at least 18 years old and have a confirmed diagnosis of relapsed or refractory B-cell lymphoma with the specific genetic changes mentioned. They also need to have received one to three previous treatments for their cancer and have measurable disease that can be tracked during the study. Participants will be carefully monitored throughout the trial, and they can expect regular check-ups to assess their health and response to the treatment. It's important to note that the trial is not yet recruiting patients, so interested individuals should stay tuned for updates on when enrollment will begin.

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ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age≥18
• • 2. Pathologically confirmed primary DLBCL or previously diagnosed indolent lymphoma (e.g., follicular lymphoma) transformation to DLBCL with TP53 deletion or mutation confirmed by FISH or next-generation sequencing.
• • 3. Received at least 1 but no more than 3 previous lines of systemic therapy for DLBCL, and was relapsed or refractory to the last line of therapy Salvage chemoimmunotherapy and subsequent stem cell transplantation are considered the same first-line systemic therapy Maintenance therapy will not be counted separately as first-line systemic therapy Radiotherapy for curative treatment of localized DLBCL lesions does not count as first-line systemic therapy
• • 4. Presence of measurable positron-emission tomography (PET) -positive lesions with at least one lymph node lesion long diameter (LDi) \> 1.5 cm or an extra-nodal lesion LDi \> 1 cm (according to the Lugano classification, 2014 version)
• • 5. Bone marrow function was good at screening Absolute neutrophil count (ANC) ≥1×109/L Platelet count ≥50×109/L (no platelet transfusion \< 14 days before cycle 1 day 1, C1D1) Hemoglobin ≥8.0 g/dL (no red blood cell transfusion \< 14 days before C1D1)
• 6. Good liver and kidney function, namely:
• • AST or ALT ≤2.5× upper normal value limit (ULN), or ≤5×ULN in the presence of known lymphoma involving the liver Serum total bilirubin ≤2×ULN, or when Gilbert's syndrome or known lymphoma involves the liver≤5×ULN CrCl≥30 mL/min according to the Cockcroft-Gault formula
• • 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• • 8. Estimated life expectancy at screening was \> 3 months
• • 9. Agree to use a highly effective contraceptive during the study, which lasts for 12 months after the last dose of study treatment
• Exclusion Criteria:
• * Patients who met any of the following exclusion criteria were not eligible for the study:
• • 1. Prior treatment with selinexor or another XPO1 inhibitor
• • 2. There are contraindications to any drug in the combination therapy
• • 3. Receipt of any standard or investigational anti-DLBCL therapy \<21 days before C1D1 (including non-palliative radiotherapy, chemotherapy, immunotherapy, radioimmunotherapy, or any other anticancer therapy) (Palliative radiotherapy for non-target lesions was allowed)
• • 4. Undergone major surgery \<14 days before C1D1
• 5. Hematopoietic stem cell transplantation /CAR-T therapy requirements are as follows:
• • Autologous hematopoietic stem cell transplantation (HSCT) \<100 days or allogeneic HSCT \<180 days prior to C1D1 Active graft-versus-host disease (GVHD) after allogeneic HSCT (or inability to discontinue GVHD therapy or preventive therapy) CAR-T cell infusion \<90 days before cycle 1
• • 6. Presence of grade ≥2 neuropathy (CTCAE, v.5.0)
• • 7. Presence of any life-threatening disease, medical condition, or organ system dysfunction that is considered by the investigator to be likely affecting patient safety or adherence to study procedures
• • 8. Uncontrolled (i.e., clinically unstable) infection within 7 days before the first dose of study treatment and required treatment with intravenous antibiotics, antiviral drugs or antifungal drugs; However, prophylactic use of these agents was allowed.
• • 9. Patients with active HBV, HCV, or HIV infection. Participants who were HBsAg positive and/or HBcAb positive but HBV-DNA negative, and/or HCV antibody positive but HCV-RNA negative were allowed to participate (the upper limit of normal values for HBV-DNA and HCV-RNA were based on the values available at each participating center).
• • 10. Inability to swallow tablets, presence of a malabsorption syndrome, or any other condition that may interfere with absorption of the study drug
• • 11. Lactating or pregnant women
• • 12. Unable or unwilling to sign the ICF
• • 13. Patients who were considered by the investigator to be significantly below tolerable weight
• • 14. Patients who received live attenuated vaccine within 28 days prior to the first dose of study treatment