EBV-Positive Diffuse Large B-Cell Lymphoma, NosPhase 1/2NCT05577364
Selinexor in Combination With R-CHOP Followed by Selinexor Maintenance for Untreated EBV-positive DLBCL Patients
A Phase 1/2 study testing Selinexor and R-CHOP Protocol in people with EBV-Positive Diffuse Large B-Cell Lymphoma, Nos, run by Sun Yat-sen University at 2 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- EBV-Positive Diffuse Large B-Cell Lymphoma, Nos
- What is being tested?
- Selinexor and R-CHOP Protocol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 2 sitesChina
- Study dates
- 1 Nov 2022to 28 Feb 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Patients with the infection of human immunodeficiency virus (HIV) and/or acquired Immunodeficiency syndrome.
- Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect the absorption of the study drug.
- Pregnant and lactating women, and subjects of childbearing age who do not want to use contraception.
- Mentally ill persons or persons unable to obtain informed consent.
- The investigators think that the patient is not suitable for the study.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Sun Yat-sen Universitiy Cancer Center
Guangzhou, Guangdong, 51000
Qing qing Cai, MD, 0086-20-87342823, caiqq@sysucc.org.cn
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, 200032
Rong Tao, MD. PhD., 86-13651603660, taorong@xinhuamed.com.cn
About this study
Official title: A Single-arm, Multi-center, Phase Ib/II Study of Selinexor in Combination With R-CHOP Followed by Selinexor Maintenance for Untreated EBV-positive DLBCL Patients (Xplore Trial)
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.
Read the detailed description
This is a prospective, single-arm, multi-center, phase Ib/II clinical trial to explore the maximum tolerated dose (MTD) of selinexor when combined with R-CHOP regimen for untreated EBV-positive DLBCL patients.
Phase Ib study:
Selinexor will be given orally at two different doses (40mg qw, and 60mg qw ) and combined with the R-CHOP regimen from the second cycle based on the "3+3" principle.
In the induction therapy period, 6 cycles of R-CHOP regimen and 2 cycles of rituximab in combination with selinexor are planned.
The dose limited toxicity (DLT) will be evaluated after the first cycle of selinexor in combination with R-CHOP.
Phase II study:
The phase II study of selinexor at recommended phase II dose (RP2D) dose level combined with R-CHOP regimen was conducted to explore the efficacy and safety of the combined regimen.
After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
- Being tested
- Selinexor, R-CHOP Protocol
- Keywords
- untreated, EBV-positive diffuse large B-cell lymphoma
- Medical subject headings
- Pyloric Stenosis, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Also called exportin 1 (XPO1) inhibitor
Selinexor: 40mg qw po, and 60mg qw po (phase Ib); RP2D (II study);
Selinexor is added from the second cycle of R-CHOP regimen.
R-CHOP ProtocolDrug
Also called Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone
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;
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Selinexor; Drug: R-CHOP Protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
To identify the MDT
Measured: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
Recommended Phase II Dose (RP2D)
To identify the RP2D
Measured: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
Complete response rate (CRR)
To investigate the preliminary antitumor efficacy
Measured: Up to 24 weeks.
Secondary outcomes (5)
Disease-free survival (DFS)
To investigate the preliminary antitumor efficacy
Measured: 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)
To investigate the preliminary antitumor efficacy
Measured: Up to 24 weeks.
Progression-free survival (PFS)
To investigate the preliminary antitumor efficacy
Measured: 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)
To investigate the preliminary antitumor efficacy
Measured: 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
To identify the incidence of AE and SAE
Measured: Through study completion, an average of 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2022
- Study start1 Nov 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion28 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EBV-Positive Diffuse Large B-Cell Lymphoma, NosStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Fudan University, Antengene Corporation
- Responsible party
- Principal investigator, Qingqing Cai, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05577364
- Sponsor's protocol ID
- B2022-534-01
- Status last verified
- Dec 2023
- First submitted
- 6 Oct 2022
- Last updated
- 14 Dec 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Multi-center, Phase Ib/II Study of Selinexor in Combination With R-CHOP Followed by Selinexor Maintenance for Untreated EBV-positive DLBCL Patients (Xplore Trial)
- ClinicalTrials.gov ID
- NCT05577364
- Acronym / sponsor ID
- B2022-534-01
- Keywords
- untreated, EBV-positive diffuse large B-cell lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Fudan University, Antengene Corporation
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 28 Feb 2026 (estimated)
- First posted
- 13 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective, single-arm, multi-center, phase Ib/II clinical trial to explore the maximum tolerated dose (MTD) of selinexor when combined with R-CHOP regimen for untreated EBV-positive DLBCL patients.
Phase Ib study:
Selinexor will be given orally at two different doses (40mg qw, and 60mg qw ) and combined with the R-CHOP regimen from the second cycle based on the "3+3" principle.
In the induction therapy period, 6 cycles of R-CHOP regimen and 2 cycles of rituximab in combination with selinexor are planned.
The dose limited toxicity (DLT) will be evaluated after the first cycle of selinexor in combination with R-CHOP.
Phase II study:
The phase II study of selinexor at recommended phase II dose (RP2D) dose level combined with R-CHOP regimen was conducted to explore the efficacy and safety of the combined regimen.
After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Selinexor in Combination With R-CHOP | Experimental | Drug: Selinexor, Drug: R-CHOP ProtocolPatients 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelinexorAlso: exportin 1 (XPO1) inhibitorSelinexor: 40mg qw po, and 60mg qw po (phase Ib); RP2D (II study); Selinexor is added from the second cycle of R-CHOP regimen. | Drug | Selinexor in Combination With R-CHOP |
| R-CHOP ProtocolAlso: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, PrednisoneRituximab: 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; | Drug | Selinexor in Combination With R-CHOP |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
To identify the MDT
Recommended Phase II Dose (RP2D)
Time frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
To identify the RP2D
Complete response rate (CRR)
Time frame: Up to 24 weeks.
To investigate the preliminary antitumor efficacy
5 secondary outcomes
Disease-free survival (DFS)
Time frame: 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)
Time frame: Up to 24 weeks.
Progression-free survival (PFS)
Time frame: 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)
Time frame: 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
Time frame: Through study completion, an average of 2 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Selinexor and R-CHOP Protocol in people with EBV-Positive Diffuse Large B-Cell Lymphoma, Nos, run by Sun Yat-sen University at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Qingqing Cai, MD. PhD. (0086-20-87342823, caiqq@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2023.