Diffuse Large B Cell LymphomaPhase 2NCT05290090
ZR2 Followed by Immunochemotherapy in Elderly Patients With Newly-diagnosed DLBCL
A Phase 2 study testing Rituximab, Lenalidomide, Zanubrutinib and RCHOP in people with Diffuse Large B Cell Lymphoma, run by Zhejiang Cancer Hospital at 1 site in China.
Trial summary
As the most common subtype of lymphoma, diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy. The poor prognosis of elderly DLBCL patients may be related to the biological behavior of the disease, more comorbidities, poor performance status, and inability to tolerate… Read more about this study
- Who is it for?
- Ages 65 to 85 years
- Conditions the study is for
- Diffuse Large B Cell Lymphoma
- What is being tested?
- Rituximab, Lenalidomide, Zanubrutinib and RCHOP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2021to 1 Dec 2025
- Phase
- Phase 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 65 to 85 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Participate in the clinical study voluntarily: fully understand and be informed of the study and sign the informed consent in person; Willing to follow and be able to complete all test procedures.
- Age: 70-85 years old, or 65-70 years old with ECOG score ≥2 points, both male and female.
- Histopathologically confirmed as diffuse large B-cell lymphoma, not otherwise specified.
- No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or biotherapy (tumor vaccine, cytokine, or anti-tumor growth factor).
- At least one evaluable or measurable lesion that meets Lugano2014 criteria (evaluable lesion: PET/CT examination showing increased uptake in lymph nodes or extranodal areas (higher than liver) and PET/CT and/or CT consistent with lymphoma; Measurable lesions: nodular lesions >15mm in length or extragendal lesions >10mm in length with increased FDG uptake).
- Adequate organ and bone marrow function, no serious hematopoietic dysfunction, abnormal heart, lung, liver, kidney function and immune deficiency (no blood transfusion, granulocytic colony stimulating factor or other relevant medical support within 14 days prior to the use of the study drug) :
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- neutrophil absolute count (ANC) ≥1.5×109/L (1500/mm3), platelet ≥75×109/L, hemoglobin ≥100g/L (if bone marrow is involved, platelet ≥50×109/L, ANC ≥1.0×109/L, hemoglobin ≥80g/L).
- Liver function: serum bilirubin ≤2.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 times the upper limit of normal value (AST or ALT≤5 times the upper limit of normal value is allowed if liver is involved).
- Renal function: creatinine clearance ≥60 mL/min (estimated according to the Cockcroft-Gault formula).
- Coagulation function: INR≤1.5 times the upper limit of normal value; PT and APTT≤1.5 times the upper limit of normal value.
- Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination.
- Negative serum pregnancy test and effective contraceptive use from signing informed consent until 6 months after the last chemotherapy.
- Life expectancy > 3 months.
Who cannot join
- Pathological subtypes: primary central nervous system diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, high-grade B-cell lymphoma, not otherwise specified. EBV positive diffuse large B-cell lymphoma
- Hemophagocytic syndrome at the time of diagnosis.
- Central nervous system involvement secondary to lymphoma.
- Participating in other clinical studies.
- Medical history of other active malignancy within 2 years prior to enrollment, except for the following conditions:(1) adequately treated in situ of the cervix carcinoma; (2) local basal cell carcinoma or squamous cell carcinoma of skin; (3) Pre-existing malignant disease that is under control and has undergone local radical treatment (surgical or other forms).
- History of Human Immunodeficiency Virus (HIV) infection and/or acquired Immunodeficiency syndrome. Patients with positive hepatitis B surface antigen or hepatitis C virus antibody must be tested hepatitis B virus DNA (no more than 1000 iu/ml) and HCV RNA detection (below the detection limit). Patients with hepatitis B virus carriers, or stabilized hepatitis B with anti-virus treatment and cured hepatitis C can be included.
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- Major surgery was performed within 28 days prior to study initiation.
- Any active infection, including bacterial, fungal or viral infections, that requires systemic antiinfection therapy within 14 days prior to treatment.
- Accompanied with severe or uncontrolled disease, including symptomatic of congestive heart failure, uncontrolled hypertension, unstable angina, active peptic ulcer or A history of severe hemorrhagic diseases, such as hemophilia A, hemophilia B, von willebrand disease or blood transfusion or other medical intervention history of spontaneous bleeding.
- History of stroke or intracranial hemorrhage within 6 months prior to first administration of the study drug.
- History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months.
- Patients who must take antiplatelet drugs and anticoagulants at the same time due to underlying diseases, and there is no alternative treatment plan.
- Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is required. Patients were excluded if they had taken a CYP3A potent or moderate-acting inhibitor or inducer within 7 days prior to the first administration of the study drug (or had taken these drugs for less than 5 half-lives).
- Hypersensitivity to the experimental drug is known.
- Patients deemed unsuitable for the study by researchers.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Haiyan Yang, PhD, 0086-571-88122192, yanghy@zjcc.org.cn
Xi Chen, MD, 0086-571-88122192, zjuchenxi@126.com
About this study
Official title: Prospective, Single-arm, Phase II Clinical Study of Rituximab, Lenalidomide, and Zanubrutinib Combination Regimen Followed by Immunochemotherapy in the Treatment of Elderly Patients With Newly-diagnosed Diffuse Large B-cell Lymphoma
As the most common subtype of lymphoma, diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy. The poor prognosis of elderly DLBCL patients may be related to the biological behavior of the disease, more comorbidities, poor performance status, and inability to tolerate standard-intensity immunochemotherapy. The investigators plan to use ZR2 regimen(rituximab, lenalidomide and zanubrutinib) for 2 cycles followed by immunochemotherapy for up to 4 cycles in elderly newly diagnosed DLBCL patients.
Read the detailed description
DLBCL mostly occurs in the elderly, with a median age at diagnosis of 66 years. Age over 60 years is a poor prognostic factor for DLBCL and is included in the International Prognostic Index (IPI) to stratify patients for prognosis. So there is an unmet need for treatment in this population. Both lenalidomide and BTK inhibitor single drugs have shown certain efficacy in DLBCL patients, and many studies have also explored the effectiveness of rituximab, lenalidomide and BTK inhibitor combination regimen in the treatment of DLBCL. Therefore, the investigators plan to use ZR2 regimen(rituximab, lenalidomide and zanubrutinib) for 2 cycles to reduce tumor burden, improve the patient's physical condition, and improve the tolerance to immunochemotherapy in elderly newly diagnosed DLBCL patients. Up to 4 cycles of immunochemotherapy were then administered sequentially in order to reduce the overall chemotherapy intensity of the patients and improve the long-term quality of life of the patients.
- Conditions
- Diffuse Large B Cell Lymphoma
- Being tested
- Rituximab, Lenalidomide, Zanubrutinib and RCHOP
- Keywords
- diffuse large B cell lymphoma, elderly, rituximab, lenalidomide, zanubrutinib, treatment, chemo-free
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab, Lenalidomide, Zanubrutinib and RCHOPDrug
Also called BGB-3111
chemo free period (21 days as a cycle, a total of 2 cycles): rituximab 375mg/m2, d1, lenalidomide 10mg qd d1-10, zanubrutinib 160mg bid.
Immunochemotherapy period: RCHOP regimen (21 days as 1 cycle, a total of 4 cycles): rituximab 375mg/m2 d0, cyclophosphamide: 750mg/m2 d1, epirubicin: 75mg/m2 d1 (or liposomal doxorubicin 35mg/m2 d1), vindesine 4mg d1, prednisone: 100mg, d1-5.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab, lenalidomide, zanubrutinib and RCHOP | Experimental | Rituximab, lenalidomide, zanubrutinib for 2 cycles: rituximab 375mg/m2, d1, lenalidomide 10mg qd d1-10, zanubrutinib 160mg bid.
RCHOP for 4 cycles: rituximab 375mg/m2 d0, cyclophosphamide: 750mg/m2 d1, epirubicin: 75mg/m2 d1 (or liposomal doxorubicin 35mg/m2 d1), vindesine 4mg d1, prednisone: 100mg, d1-5. Receives: Drug: Rituximab, Lenalidomide, Zanubrutinib and RCHOP |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
overall response rate
Measured: 21days after the end of treatment
Secondary outcomes (5)
PFS
Progression Free Survival
Measured: From date of first day of treatment until the date of first documented progression, assessed up to 24 months
OS
Overall Survival
Measured: From date of first day of treatment until the date of first documented date of death from any cause, assessed up to 24 months
AE and SAE
Adverse event and serious adverse event
Measured: From date of first day of treatment until 30 day after last treatment
Performance status
Assess the patient's performance status according to the Barthel index. Patients will be classified into 5 scales with the score ranging from 0 to 100: 0-20 points=extremely severe functional impairment; 25-45 points=severe functional impairment; 50-70 points=moderate functional impairment; 75-95 points=mild functional impairment; 100 points=normal. Higher scores mean a better outcome.
Measured: At screening period, after 2 cycles of ZR2 regimen(each cycle is 21 days), after 2 cycles of RCHOP regimen(each cycle is 21 days) and 21days after the end of treatment
Life quality
Assess the patient's quality of life according to the EORTC QLQ-C30 questionnaire. Higher scores mean a worse outcome.
Measured: At screening period, after 2 cycles of ZR2 regimen(each cycle is 21 days), after 2 cycles of RCHOP regimen(each cycle is 21 days) and 21days after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2022
- Study start1 Oct 2021
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Zhejiang Cancer HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yang haiyan, Zhejiang Cancer Hospital
- Investigators
- Haiyan Yang, Principal investigator, Zhejiang Cancer Hospital, Hangzhou, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05290090
- Sponsor's protocol ID
- ZR2+RCHOP
- Status last verified
- Oct 2023
- First submitted
- 28 Jan 2022
- Last updated
- 17 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Single-arm, Phase II Clinical Study of Rituximab, Lenalidomide, and Zanubrutinib Combination Regimen Followed by Immunochemotherapy in the Treatment of Elderly Patients With Newly-diagnosed Diffuse Large B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT05290090
- Acronym / sponsor ID
- ZR2+RCHOP
- Conditions
- Diffuse Large B Cell Lymphoma
- Keywords
- diffuse large B cell lymphoma, elderly, rituximab, lenalidomide, zanubrutinib, treatment, chemo-free
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- Zhejiang Cancer HospitalUniversity, hospital or other
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 22 Mar 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.
As the most common subtype of lymphoma, diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy. The poor prognosis of elderly DLBCL patients may be related to the biological behavior of the disease, more comorbidities, poor performance status, and inability to tolerate standard-intensity immunochemotherapy. The investigators plan to use ZR2 regimen(rituximab, lenalidomide and zanubrutinib) for 2 cycles followed by immunochemotherapy for up to 4 cycles in elderly newly diagnosed DLBCL patients.
Detailed description
DLBCL mostly occurs in the elderly, with a median age at diagnosis of 66 years. Age over 60 years is a poor prognostic factor for DLBCL and is included in the International Prognostic Index (IPI) to stratify patients for prognosis. So there is an unmet need for treatment in this population. Both lenalidomide and BTK inhibitor single drugs have shown certain efficacy in DLBCL patients, and many studies have also explored the effectiveness of rituximab, lenalidomide and BTK inhibitor combination regimen in the treatment of DLBCL. Therefore, the investigators plan to use ZR2 regimen(rituximab, lenalidomide and zanubrutinib) for 2 cycles to reduce tumor burden, improve the patient's physical condition, and improve the tolerance to immunochemotherapy in elderly newly diagnosed DLBCL patients. Up to 4 cycles of immunochemotherapy were then administered sequentially in order to reduce the overall chemotherapy intensity of the patients and improve the long-term quality of life of the patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab, lenalidomide, zanubrutinib and RCHOP | Experimental | Drug: Rituximab, Lenalidomide, Zanubrutinib and RCHOPRituximab, lenalidomide, zanubrutinib for 2 cycles: rituximab 375mg/m2, d1, lenalidomide 10mg qd d1-10, zanubrutinib 160mg bid. RCHOP for 4 cycles: rituximab 375mg/m2 d0, cyclophosphamide: 750mg/m2 d1, epirubicin: 75mg/m2 d1 (or liposomal doxorubicin 35mg/m2 d1), vindesine 4mg d1, prednisone: 100mg, d1-5. |
Who may qualify
- Ages
- 65 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (13 listed)
- Participate in the clinical study voluntarily: fully understand and be informed of the study and sign the informed consent in person; Willing to follow and be able to complete all test procedures.
- Age: 70-85 years old, or 65-70 years old with ECOG score ≥2 points, both male and female.
- Histopathologically confirmed as diffuse large B-cell lymphoma, not otherwise specified.
- No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or biotherapy (tumor vaccine, cytokine, or anti-tumor growth factor).
- At least one evaluable or measurable lesion that meets Lugano2014 criteria (evaluable lesion: PET/CT examination showing increased uptake in lymph nodes or extranodal areas (higher than liver) and PET/CT and/or CT consistent with lymphoma; Measurable lesions: nodular lesions >15mm in length or extragendal lesions >10mm in length with increased FDG uptake).
Key exclusion criteria (15 listed)
- Pathological subtypes: primary central nervous system diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, high-grade B-cell lymphoma, not otherwise specified. EBV positive diffuse large B-cell lymphoma
- Hemophagocytic syndrome at the time of diagnosis.
- Central nervous system involvement secondary to lymphoma.
- Participating in other clinical studies.
- Medical history of other active malignancy within 2 years prior to enrollment, except for the following conditions:(1) adequately treated in situ of the cervix carcinoma; (2) local basal cell carcinoma or squamous cell carcinoma of skin; (3) Pre-existing malignant disease that is under control and has undergone local radical treatment (surgical or other forms).
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 |
|---|---|---|
| Rituximab, Lenalidomide, Zanubrutinib and RCHOPAlso: BGB-3111chemo free period (21 days as a cycle, a total of 2 cycles): rituximab 375mg/m2, d1, lenalidomide 10mg qd d1-10, zanubrutinib 160mg bid. Immunochemotherapy period: RCHOP regimen (21 days as 1 cycle, a total of 4 cycles): rituximab 375mg/m2 d0, cyclophosphamide: 750mg/m2 d1, epirubicin: 75mg/m2 d1 (or liposomal doxorubicin 35mg/m2 d1), vindesine 4mg d1, prednisone: 100mg, d1-5. | Drug | Rituximab, lenalidomide, zanubrutinib and RCHOP |
Primary outcome
ORR
Time frame: 21days after the end of treatment
overall response rate
5 secondary outcomes
PFS
Time frame: From date of first day of treatment until the date of first documented progression, assessed up to 24 months
OS
Time frame: From date of first day of treatment until the date of first documented date of death from any cause, assessed up to 24 months
AE and SAE
Time frame: From date of first day of treatment until 30 day after last treatment
Performance status
Time frame: At screening period, after 2 cycles of ZR2 regimen(each cycle is 21 days), after 2 cycles of RCHOP regimen(each cycle is 21 days) and 21days after the end of treatment
Life quality
Time frame: At screening period, after 2 cycles of ZR2 regimen(each cycle is 21 days), after 2 cycles of RCHOP regimen(each cycle is 21 days) and 21days after the end of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2023.
- Individual participant dataSharing planned: No
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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.
Haiyan Yang principal investigator
Zhejiang Cancer Hospital, Hangzhou, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab, Lenalidomide, Zanubrutinib and RCHOP in people with Diffuse Large B Cell Lymphoma, run by Zhejiang Cancer Hospital at 1 site 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 13 inclusion and 15 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 17 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 phase mean?
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 xi chen (17816890591, zjuchenxi@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: 21days after the end of treatment). 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 17 Oct 2023.