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

NCT05422066 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ATG-010-MA-CL-DLBCL-002
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

Brief Summary

This is a phase II, multicenter, single-arm and open-label study to explore Selinexor in combination with standard of care R-CHOP in New Diagnosed high-risk GCB-subtype DLBCL (IPI 3-5). Approximately 35 patients plan to be enrolled in about 6-8 study sites of the study. And the objective is to Evaluate the safety and efficacy of XR-CHOP in High-Risk (IPI 3-5) GCB-subtype DLBCL.The enrollment period for this study is expected to be approximately 18 months. The study will end when all patients have completed 6 cycles treatment/follow-up since the initiation of the study drug, or the last patient has expired, has been lost to follow-up, or has withdrawn consent, whichever occurs first.

Conditions

DLBCL Germinal Center B-Cell Type

Keywords

Selinexor; Xpovio; Newly Diagnosed; DLBCL; IPI 3-5

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CR)

  Complete Remission (CR) rate at any time up of cycle 6 defined by Lugano 2014 defined response. Number of patients who achieved complete response after treatment by XR-CHOP

  up to 18 months

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  up to 18 months

• Progression Free Survival(PFS)

  up to 18 months

• Disease free survival(DFS)

  up to 18 months

• Overall survival(OS)

  up to 18 months

• Safety/toxicity profile

  From start of study drug administration up to 30 days after last dose of study treatment

Study Arms (1)

Selinexor-R-CHOP

EXPERIMENTAL

Selinexor po 60mg once weekly, Rituximab iv 375 mg/sqm on day 1, Cyclophosphamide iv 750 mg/sqm on day 1, Doxorubicin iv 50 mg/sqm on day 1, Vincristine iv 0.5 mg/kg on day 1, Prednisone po 100mg on days 1-5 in a 21 days per cycle.

Drug: Selinexor; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Interventions

Selinexor DRUG

Selinexor (ATG-010# is a first-in-class, oral selective exportin 1 (XPO1) inhibitor (1,2). Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus along with inhibition of translation of oncoprotein mRNAs. Selinexor 60mg on day 1,8,15 for 21 days cycles

Also known as: ATG-010, Xpovio

Selinexor-R-CHOP

Rituximab DRUG

Induction Chemotherapy: 375mg/sqm, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease, up to 6 cycles.

Also known as: RiTUXimab Injection

Selinexor-R-CHOP

Cyclophosphamide DRUG

Induction Chemotherapy: 750mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease, up to 6 cycles.

Also known as: Cyclophosphamide Injection

Selinexor-R-CHOP

Doxorubicin DRUG

Induction Chemotherapy: 70mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease, up to 6 cycles.

Also known as: Doxorubicin Hydrochloride

Selinexor-R-CHOP

Vincristine DRUG

Induction Chemotherapy: 1.4mg/m2 (Max: 2mg), Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease, up to 6 cycles.

Also known as: Vincristine Injection

Selinexor-R-CHOP

Prednisone DRUG

Induction Chemotherapy: 100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease, up to 6 cycles.

Also known as: Prednisone Oral Product

Selinexor-R-CHOP

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to written informed consent (ICF) .
• Age ≥ 18 years and ≤ 75 years.
• Histologically confirmed Diffuse Large B-Cell Lymphoma of the germinal center B-cell(DLBCL) subtype by Hans.
• Patients no prior chemotherapy or radiotherapy for DLBCL, with the exception of no more than 5 days of treatment with glucocorticoids for symptom control.
• International Prognostic Index score of 3-5.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• 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).
• Absolute neutrophil count (ANC)≥1.5×109/L;
• 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.
• Hemoglobin (HB)≥85g/L(no red blood cell transfusion within 14 days prior to C1D1).
• Adequate hepatic and renal function:
• 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),
• Serum total bilirubin ≤2×ULN, or Serum total bilirubin ≤5×ULN if due to Gilbert syndrome or lymphoma involvement.
• Estimated creatinine clearance ≥ 30 mL/min (calculated using the formula of Cockroft-Gault).

You may not qualify if:

• Willing and able to written informed consent (ICF) .
• Age ≥ 18 years and ≤ 75 years.
• Histologically confirmed Diffuse Large B-Cell Lymphoma of the germinal center B-cell(DLBCL) subtype by Hans.
• Patients no prior chemotherapy or radiotherapy for DLBCL, with the exception of no more than 5 days of treatment with glucocorticoids for symptom control.
• International Prognostic Index score of 3-5.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• 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).
• Absolute neutrophil count (ANC)≥1.5×109/L;
• 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.
• Hemoglobin (HB)≥85g/L(no red blood cell transfusion within 14 days prior to C1D1).
• Adequate hepatic and renal function:
• 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),
• Serum total bilirubin ≤2×ULN, or Serum total bilirubin ≤5×ULN if due to Gilbert syndrome or lymphoma involvement.
• Estimated creatinine clearance ≥ 30 mL/min (calculated using the formula of Cockroft-Gault).

Sponsors & Collaborators

• Li Zhiming: lead
• Antengene Corporation: collaborator

Study Sites (6)

Department of Medical Oncology, Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

NOT YET RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

NOT YET RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

NOT YET RECRUITING

The Affiliated People's Hospital of Ningbo University

Ningbo, Zhejiang, 315000, China

NOT YET RECRUITING

MeSH Terms

Interventions

selinexor; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Zhiming Li, Ph.D

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiming Li, Ph.D

CONTACT

+86-020-87343765; lizhm@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician, professor

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: June 16, 2022
• Study Start: July 26, 2022
• Primary Completion: July 30, 2025
• Study Completion: December 31, 2025
• Last Updated: June 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Study Protocol can be shared Starting 12 months after publication
• Access Criteria: Study Protocol must not be shared with non-participants until after publication and must be authorized by the principal investigator and sponsors

Locations

CN (6)