Status:

NOT_YET_RECRUITING

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

Lead Sponsor:

Ruijin Hospital

Conditions:

Relapsed or Refractory B-cell Lymphoma

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

To evaluate the efficacy and safety of selinexor combined with R-GDP regimen in the treatment of patients with TP53-altered relapsed or refractory B-cell lymphoma.

Detailed Description

This study is a single-arm, open-label exploratory clinical trial. To evaluate the efficacy and safety of selinexor combined with R-GDP regimen in the treatment of patients with TP53-altered relapsed ...

Eligibility Criteria

Inclusion

  • Age≥18
  • 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.
  • 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
  • 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)
  • 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)
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Estimated life expectancy at screening was \> 3 months
  • Agree to use a highly effective contraceptive during the study, which lasts for 12 months after the last dose of study treatment

Exclusion

  • Patients who met any of the following exclusion criteria were not eligible for the study:
  • Prior treatment with selinexor or another XPO1 inhibitor
  • There are contraindications to any drug in the combination therapy
  • 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)
  • Undergone major surgery \<14 days before C1D1
  • 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
  • Presence of grade ≥2 neuropathy (CTCAE, v.5.0)
  • 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
  • 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.
  • 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).
  • Inability to swallow tablets, presence of a malabsorption syndrome, or any other condition that may interfere with absorption of the study drug
  • Lactating or pregnant women
  • Unable or unwilling to sign the ICF
  • Patients who were considered by the investigator to be significantly below tolerable weight
  • Patients who received live attenuated vaccine within 28 days prior to the first dose of study treatment

Key Trial Info

Start Date :

October 30 2023

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

September 30 2027

Estimated Enrollment :

50 Patients enrolled

Trial Details

Trial ID

NCT06062641

Start Date

October 30 2023

End Date

September 30 2027

Last Update

November 7 2023

Active Locations (1)

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Ruijin Hospital

Shanghai, Shanhai, China, 200025