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

NCT06062641 | Not Yet Recruiting Phase 2

• 1 other identifier: RJ-XLYM-002
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsed or Refractory B-cell Lymphoma

Keywords

TP53-altered; Relapsed/Refractory; Diffuse Large B Cell Lymphoma; Selinexor

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective Response Rate (ORR) : The investigator-assessed best disease status of patients with TP53-altered R/R DLBCL was the rate of Complete Response (CR) or Partial Response (PR)

  At the end of Cycle 6 (each cycle is 21 days)

Secondary Outcomes (3)

• progression free survival

  Baseline up to data cut-off (up to approximately 2 years)

• overall survival

  Baseline up to data cut-off (up to approximately 2 years)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  Up to 30 days after completion of study treatment

Study Arms (1)

SR-GDP

EXPERIMENTAL

Drug: SR-GDP

Interventions

SR-GDP DRUG

Selinexor 40mg/d，po d1,8,15; rituximab 375mg/m2, iv d1; gemcitabine 1g/m2, iv d1,8; cisplatin 25mg/m2, iv d1-3; dexamethasone 40mg，po/iv d1-4 (If patient\>70y, the dosage should be changed to 20mg). Each cycle lasts for 21 days, with a maximum of 6 cycles of combination therapy. For patients who achieved PR or better response at the end of combination therapy, they will start receiving single-agent selinexor 40mg treatment (qw) in cycles of 28 days until disease progression (PD) or unacceptable toxicity occurs.

SR-GDP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital

Shanghai, Shanhai, 200025, China

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Weili Zhao, PhD, MD

  Ruijin Hospital

  STUDY CHAIR

Central Study Contacts

Weili Zhao, PhD, MD

CONTACT

+862164370045; zwl_trial@163.com

Li Wang, PhD, MD

CONTACT

+862164370045; wl_wangdong@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice president，Ruijin hospital

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 2, 2023
• Study Start: October 30, 2023
• Primary Completion: April 30, 2024
• Study Completion (Estimated): September 30, 2027
• Last Updated: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)