Selinexor in Combination With R-CHOP Followed by Selinexor Maintenance for Untreated EBV-positive DLBCL Patients

NCT05577364 | Recruiting Phase 1

• 1 other identifier: B2022-534-01
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

This is a prospective, single-arm, multi-center, phase Ib/II clinical trial to evaluate the safety, tolerability, and efficacy of selinexor in combination with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) followed by selinexor maintenance for untreated EBV-positive diffuse large B-cell lymphoma (DLBCL) patients.

Conditions

EBV-Positive Diffuse Large B-Cell Lymphoma, Nos

Keywords

untreated, EBV-positive diffuse large B-cell lymphoma

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  To identify the MDT

  The first cycle of selinexor in combination with R-CHOP regimen (21 days)

• Recommended Phase II Dose (RP2D)

  To identify the RP2D

  The first cycle of selinexor in combination with R-CHOP regimen (21 days)

• Complete response rate (CRR)

  To investigate the preliminary antitumor efficacy

  Up to 24 weeks.

Secondary Outcomes (5)

• Disease-free survival (DFS)

  From date of the first complete response until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• Objective response rate (ORR)

  Up to 24 weeks.

• Progression-free survival (PFS)

  From date of the first injection until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• Overall survival (OS)

  From date of the first injection until the date of death from ant cause, assessed up to 24 months

• Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0

  Through study completion, an average of 2 years.

Other Outcomes (4)

• The correlation between EBV-DNA level and efficacy indicators, such as CRR, DFS, ORR, PFS, and OS

  Through study completion, an average of 2 years.

• The gene mutations such as DDX3X、TET2、PTPN2 and so on are sequenced by whole genome sequencing.

  Through study completion, an average of 2 years.

• The mRNA and lncRNA alterations are sequenced by transcriptome sequencing.

  Through study completion, an average of 2 years.

Study Arms (1)

Selinexor in Combination With R-CHOP

EXPERIMENTAL

Patients with untreated EBV-positive diffuse large B-cell lymphoma will receive sequentially higher doses of selinexor in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle).The initial dose of selinexor is 40mg qw po. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.

Drug: Selinexor; Drug: R-CHOP Protocol

Interventions

Selinexor DRUG

Selinexor: 40mg qw po, and 60mg qw po (phase Ib); RP2D (II study); Selinexor is added from the second cycle of R-CHOP regimen.

Also known as: exportin 1 (XPO1) inhibitor

Selinexor in Combination With R-CHOP

R-CHOP Protocol DRUG

Rituximab: 375mg/m2 iv.drip D1; Cyclophosphamide: 750mg/m2 iv.drip D1; Doxorubicin: 50mg/m2 iv.drip D1; Vincristine: 1.4g/m2 iv D1; Prednisone: 100mg po D1-5;

Also known as: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

Selinexor in Combination With R-CHOP

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects fully understand and voluntarily participate in this study and sign informed consent
• Age ≥18, ≤70 years, no gender limitation.
• Histologically confirmed diagnosis of EBV-positive diffuse large B-cell lymphoma (DLBCL) (more than 50% of tumor cells are positive with EBV encoded small RNAs (EBERs) in situ hybridization were considered EBERs positive).
• Untreated patients, except for the short-time use of prednisone for controlling tumor-induced symptoms (no more than 30mg/d (or other equivalent amounts of other glucocorticoids), no more than 7 days).
• There must be at least one measurable or evaluable lesion that meets the evaluation criteria for Lugano 2014 lymphoma: measurable lesion: Positron emission tomography/computed tomography (PET/CT) or CT and/or MRI, intranodal lesions with long diameter \>1.5cm, and short diameter \>1.0cm, or extranodal lesions with long diameter \> 1.0 cm.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
• Expected survival ≥ 3 months.
• Adequate function of bone marrow:
• White blood cell ≥3.0×10E9/L, absolute neutrophil count ≥1.5×10E9/L Platelet ≥100×10E9/L (Bone marrow invasive patient≥75×109/L) Hemoglobin≥ 90g/L No granulocyte growth factor, platelet, or red blood cell transfusions were received within 14 days prior to examination.
• Adequate function of the liver and renal:
• Total bilirubin≤2×upper limit of normal (ULN) (patients with liver invasion or Gilbert syndrome ≤5×ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (patients with liver invasion ≤5×ULN) Serum creatinine ≤1.5×ULN or creatinine clearance rate ≥60 mL/min
• The patients agree to take effective contraceptive measures during the study period and till 12 months after the last administration of the study treatment.

You may not qualify if:

• EBV-positive DLBCL combined with other types of lymphoma. Transformed DLBCL.
• EBV-positive DLBCL with central nervous system invasion.
• The patients had previously received XPO1 inhibitors, such as selinexor and so on.
• The patients have contraindications to any drug in the combined treatment.
• The major surgery is performed within 4 weeks before enrollment, except for diagnosis.
• There are any life-threatening diseases, medical conditions or organ system dysfunction that the investigator believes may affect the safety or compliance of patients.
• Heart function and disease meet one of the following conditions:
• Heart failure with the classification of New York Heart Association heart function of grade II;
• A history of unstable angina pectoris;
• A history of myocardial infarction within the past 1 years;
• Patients with clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention;
• A history of other malignant tumors within the past 5 years (except the cured cervical cancer and basal cell carcinoma of the skin).
• Patients with active bleeding.
• Uncontrolled infection exists within 7 days before treatment and parenteral antibiotics, antiviral drugs or antifungal drugs are needed; However, preventive use of these drugs (including parenteral anti-infective drugs) is allowed.
• Patients with chronic active hepatitis B or active hepatitis C. If the background hepatitis B Surface Antigen (HBsAg) and/or hepatitis B core Antibody (HBcAb) or hepatitis C Virus (HCV) antibody are positive, the further determination for Hepatitis B Virus (HBV) DNA (no more than 2500 copies /mL or 500 IU/mL) and HCV RNA (no more than the lower limit of the assay) can be included. The patients with HBsAg and/or HBcAb positive need to receive anti-HBV drugs.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Fudan University: collaborator
• Antengene Corporation: collaborator

Study Sites (2)

Sun Yat-sen Universitiy Cancer Center

Guangzhou, Guangdong, 51000, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

RECRUITING

MeSH Terms

Conditions

Pyloric Stenosis, Hypertrophic

Interventions

selinexor; Exportin 1 Protein; R-CHOP protocol; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Karyopherins; Nucleocytoplasmic Transport Proteins; Membrane Transport Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins; Nuclear Proteins; Receptors, Cytoplasmic and Nuclear; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood 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

Central Study Contacts

Qingqing Cai, MD. PhD.

CONTACT

0086-20-87342823; caiqq@sysucc.org.cn

Huiqiang Huang, MD. PhD.

CONTACT

0086-20-87342823; huanghq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 13, 2022
• Study Start: November 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: February 28, 2026
• Last Updated: December 14, 2023

Record last verified: 2023-12

Locations

CN (2)