Diffuse Large B-cell LymphomaPhase 2NCT05257018
R-CDOP Combined With Intrathecal Methotrexate for DLBCL Patients With High-risk of CNS Relapse
A Phase 2 study testing R-CDOP+intrathecal MTX in people with Diffuse Large B-cell Lymphoma, run by Fudan University at 2 sites in China.
Trial summary
This is a double-center, single-arm, phase 2 study to evaluate the efficacy and safety of R-CDOP regimen combined with intrathecal methotrexate in chemo-naive diffuse large B-cell lymphoma patients with high-risk of CNS relapse. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- R-CDOP+intrathecal MTX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 2 sitesChina
- Study dates
- 26 Feb 2022to 30 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age range from 18 to 75 years;
- ECOG performance status: 0-2;
- Histopathologically confirmed untreated diffuse large B-cell lymphoma (cell origin can be distinguished according to Hans algorithm) , And fulfilled the following criteria for high-risk CNS recurrence:
- CNS-IPI 4-6;
- The lymphoma involved testis, breast (excluding unilateral breast and less than 5 cm mass), adrenal gland, kidney, paranasal sinus, paravertebral, and bone marrow and other sites;
- PCLBCL-leg;
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- Subjects have at least one measurable lesion: the long axis of the lymph node shall be>1.5 cm, the long axis of the extranodal lesions shall be>1.0 cm;
- Bone marrow hematopoiesis was essentially normal: WBC≥3.5 ×10^9/L, ANC≥1.5×10^9/L, PLT≥80×10^9/L, Hb≥90 g/L. Abnormal peripheral blood indices, as a result of lymphoma invading the bone marrow or spleen, permitted enrollment at the discretion of the investigator;
- Liver function: total bilirubin, ALT, AST < 1.5×UNL (upper limit of normal);
- Renal function: Cr < 1.5×UNL and creatinine clearance≥30 ml/min;
- Echocardiography or nuclide cardiac function testing with LVEF≥50%;
- Patients in the reproductive period agreed to appropriate contraception. Women in the reproductive period had a negative serum pregnancy test within 2 weeks before enrollment;
- Consent to provide pathological tissue specimens (wax blocks within half a year or 20 slides for paraffin tissue sections);
- Life expectancy≥3 months;
- Signed informed consent;
Who cannot join
- Patients with a known history of severe allergy to humanized or murine mAbs, or any contraindication to R-CDOP, intrathecal MTX;
- Patients with evidence of CNS involvement (baseline cerebrospinal fluid, imaging, symptoms);
- Special types of diffuse large B-cell lymphoma patients who are not suitable for induction therapy with R-CDOP, such as PMBCL, double-hit large B-cell lymphoma, etc;
- Clinically significant cardiac conditions, including severe cardiac insufficiency: New York Heart Association (NYHA) cardiac insufficiency class IV, unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and Q-Tc interval greater than 500 ms;
- Those who had a second degree or greater operation within three weeks before treatment;
- Diagnosed with a malignancy other than lymphoma or under treatment, with the following exceptions:
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- Had received treatment with curative intent and had not developed malignancy with known active disease ≥ 5 years prior to enrollment;
- Basal cell carcinoma of the skin (other than melanoma) that has been adequately treated with no evidence of disease;
- Carcinoma in situ of the cervix that has been adequately treated with no evidence of disease;
- Had significant coagulation abnormalities;
- Any previous antilymphoma therapy other than short-term corticosteroids (up to 10 days);
- Those with severe active infection;
- Other serious, uncontrolled concomitant conditions that may affect protocol adherence or interfere with interpretation of results include uncontrolled diabetes mellitus, or pulmonary disease (interstitial pneumonia, obstructive pulmonary disease, and a history of symptomatic bronchospasm), hypertension, and others;
- HBV (HBsAg positive and HBV-DNA ≥ 104 IU / ml), HCV (HCV antibody positive and HCV-RNA measurable); And subjects with other acquired, congenital immunodeficiency diseases, including but not limited to those with HIV infection;
- Pregnant or lactating women;
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Junning Cao, doctor contact
China2 sites, 2 recruiting
- Recruiting
Dongmei Ji
Shanghai, Shanghai Municipality, 021
dongmei ji, doctor
dongmei ji, 13564183928, jidongmei2000@126.com
- Not yet recruiting
Cancer Hospital affilicaited to Xinjiang Medical University
Ürümqi, Xinjiang
Shujuan Wen, Doctor
Shujuan Wen, doctor
About this study
Official title: A Phase II Study of R-CDOP Combined With Intrathecal Methotrexate for Diffuse Large B-cell Lymphoma Patients With High-risk of Central Nervous System Relapse
This is a double-center, single-arm, phase 2 study to evaluate the efficacy and safety of R-CDOP regimen combined with intrathecal methotrexate in chemo-naive diffuse large B-cell lymphoma patients with high-risk of CNS relapse.
Read the detailed description
Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin's lymphoma, accounting for 31% of all non-Hodgkin's lymphomas. At present, the standard treatment is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) Regimen. In DLBCL, central nervous system recurrence is rare, but once it occurs, it is often fatal. The prognosis of patients with central recurrence of DLBCL is very poor, and the median survival time is only 3.5-7 months.The CNS relapse rate of the R-CHOP regimen combined with MTX (methotrexate) intrathecal in high CNS-IPI DLBCL patients is approximately 12%.
This study was a phase II, prospective, single arm，double-center study, which requires a total of 83 DLBCL patients with high-risk of CNS relapse.
Patients will receive a total of 6-8 cycles of R-CDOP regimen, repeated every 3 weeks. Intrathecal MTX will be administered after the 1st-5th cycle of chemotherapy. All the patients will receive a mid-treatment PET scan after 4 cycles of chemotherapy. Patient achieves CR (complete response) after 4 cycles will continue to receive another 2 cycles of treatment. For those who achieve PR, another 4 cycles of chemotherapy will given.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- R-CDOP+intrathecal MTX
- Keywords
- Chemo-naive Diffuse Large B-cell Lymphoma, Doxorubicin Hydrochloride Liposome Injection, Methotrexate, Central Nervous System Relapsed, R-CDOP, Objective Response Rate, Progression Free Survival, 2-year CNS relapse rate
- 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.
R-CDOP+intrathecal MTXDrug
Also called Pegylated liposome doxorubicin（PLD）
R-CDOP+intrathecal MTX：
- Rituximab 375 mg / m^2，D1
- Cyclophosphamide 750 mg / m^2，D2
- Doxorubicin Hydrochloride Liposome Injection 35mg / m^2，D2
- Vincristine 1.4mg/m^2 (dose capped at 2 mg)，D2
- Prednisone 50 mg， bid D2-6
- Cycle1-5：Intrathecal MTX 12 mg + DXM 5 mg after chemotherapy （PK patients will be given 24 h after chemotherapy）
| Study group | Role | What they receive |
|---|---|---|
| R-CDOP+intrathecal MTX | Experimental | R-CDOP+intrathecal MTX：
* Rituximab 375 mg / m^2，D1
* Cyclophosphamide 750 mg / m^2，D2
* Doxorubicin Hydrochloride Liposome Injection 35mg / m^2，D2
* Vincristine 1.4mg/m^2 (dose capped at 2 mg)，D2
* Prednisone 50 mg， bid D2-6
* Cycle1-5：Intrathecal MTX 12 mg + DXM 5 mg after chemotherapy （PK patients will be given 24h after chemotherapy） Receives: Drug: R-CDOP+intrathecal MTX |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year central nervous system relapse rate
The proportion of patients with central nervous system recurrence within two years from enrollment accounted for all patients treated with drugs.
Measured: up to 6 years after the start of the study
Concentration of doxorubicin in cerebrospinal fluid after using doxorubicin hydrochloride liposome injection
CSF doxorubicin concentrations 24 hours after the first 5 courses of lipso-doxorubicin infusion will be tested. Peak concentration of doxorubicin in CSF will be recorded, and the area under the curve will be calculated.
Measured: up to 4 years after the start of the study
Secondary outcomes (10)
Objective response rate (ORR)
Objective response rate measured as number of complete and partial response divided by the number of patients included.
Measured: 2 years after enrollment of final patient
2-year progression-free survival (PFS) rate
Number of non-progression cases/all enrolled cases at 2 years
Measured: 2 years after enrollment of final patient
2-year event-free survival (EFS) rate
Number of non-event cases/all enrolled cases at 2 years
Measured: 2 years after enrollment of final patient
Overall Survival (OS)
Time from the date of enrollment to data of death from any cause, or date of lost follow-up, whichever comes first, and otherwise censored at time last known alive.
Measured: 2 years after enrollment of final patient
Adverse events
Hematologic and non hematologic adverse event (CTCAE 4.03）
Measured: Since the signing of informed consent forms to 30 days after the last cycle
Cmax（maximum concentration）
The peak concentration of the drug
Measured: Time from zero to Tmax
Tmax（maximum time）
The peak time of the drug
Measured: Time from zero to Cmax
T1/2（drug half time）
The time it takes for blood concentration levels to drop by half
Measured: The time it takes for blood concentration levels to drop by half
AUC（0-∞）（area under the curve）
area under the concentration-time curve
Measured: Time from zero to ∞
AUC （0-t）（area under the curve from time zero to the last observation time
area under the concentration-time curve from time zero to the time of last area area under the concentration-time curve from time zero to the last observation time
Measured: Time from zero to the last observation time
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2022
- Study start26 Feb 2022
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2028 (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 Fudan 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 83 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ji Dongmei, Fudan University
- Investigators
- Dongmei Ji, doctor, Principal investigator, Fudan UniversityJunning Cao, Doctor, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05257018
- Sponsor's protocol ID
- CSPC-DMS-LM-K001
- Status last verified
- Mar 2026
- First submitted
- 20 Dec 2021
- Last updated
- 2 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of R-CDOP Combined With Intrathecal Methotrexate for Diffuse Large B-cell Lymphoma Patients With High-risk of Central Nervous System Relapse
- ClinicalTrials.gov ID
- NCT05257018
- Acronym / sponsor ID
- CSPC-DMS-LM-K001
- Conditions
- Diffuse Large B-cell Lymphoma
- Keywords
- Chemo-naive Diffuse Large B-cell Lymphoma, Doxorubicin Hydrochloride Liposome Injection, Methotrexate, Central Nervous System Relapsed, R-CDOP, Objective Response Rate, Progression Free Survival, 2-year CNS relapse rate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 83 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 26 Feb 2022 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 25 Feb 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 double-center, single-arm, phase 2 study to evaluate the efficacy and safety of R-CDOP regimen combined with intrathecal methotrexate in chemo-naive diffuse large B-cell lymphoma patients with high-risk of CNS relapse.
Detailed description
Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin's lymphoma, accounting for 31% of all non-Hodgkin's lymphomas. At present, the standard treatment is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) Regimen. In DLBCL, central nervous system recurrence is rare, but once it occurs, it is often fatal. The prognosis of patients with central recurrence of DLBCL is very poor, and the median survival time is only 3.5-7 months.The CNS relapse rate of the R-CHOP regimen combined with MTX (methotrexate) intrathecal in high CNS-IPI DLBCL patients is approximately 12%.
This study was a phase II, prospective, single arm，double-center study, which requires a total of 83 DLBCL patients with high-risk of CNS relapse.
Patients will receive a total of 6-8 cycles of R-CDOP regimen, repeated every 3 weeks. Intrathecal MTX will be administered after the 1st-5th cycle of chemotherapy. All the patients will receive a mid-treatment PET scan after 4 cycles of chemotherapy. Patient achieves CR (complete response) after 4 cycles will continue to receive another 2 cycles of treatment. For those who achieve PR, another 4 cycles of chemotherapy will given.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| R-CDOP+intrathecal MTX | Experimental | Drug: R-CDOP+intrathecal MTXR-CDOP+intrathecal MTX： * Rituximab 375 mg / m^2，D1 * Cyclophosphamide 750 mg / m^2，D2 * Doxorubicin Hydrochloride Liposome Injection 35mg / m^2，D2 * Vincristine 1.4mg/m^2 (dose capped at 2 mg)，D2 * Prednisone 50 mg， bid D2-6 * Cycle1-5：Intrathecal MTX 12 mg + DXM 5 mg after chemotherapy （PK patients will be given 24h after chemotherapy） |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age range from 18 to 75 years;
- ECOG performance status: 0-2;
- Histopathologically confirmed untreated diffuse large B-cell lymphoma (cell origin can be distinguished according to Hans algorithm) , And fulfilled the following criteria for high-risk CNS recurrence:
- Subjects have at least one measurable lesion: the long axis of the lymph node shall be>1.5 cm, the long axis of the extranodal lesions shall be>1.0 cm;
- Bone marrow hematopoiesis was essentially normal: WBC≥3.5 ×10^9/L, ANC≥1.5×10^9/L, PLT≥80×10^9/L, Hb≥90 g/L. Abnormal peripheral blood indices, as a result of lymphoma invading the bone marrow or spleen, permitted enrollment at the discretion of the investigator;
Key exclusion criteria (15 listed)
- Patients with a known history of severe allergy to humanized or murine mAbs, or any contraindication to R-CDOP, intrathecal MTX;
- Patients with evidence of CNS involvement (baseline cerebrospinal fluid, imaging, symptoms);
- Special types of diffuse large B-cell lymphoma patients who are not suitable for induction therapy with R-CDOP, such as PMBCL, double-hit large B-cell lymphoma, etc;
- Clinically significant cardiac conditions, including severe cardiac insufficiency: New York Heart Association (NYHA) cardiac insufficiency class IV, unstable angina, acute myocardial infarction within 6 months prior to screening, congestive heart failure, and Q-Tc interval greater than 500 ms;
- Those who had a second degree or greater operation within three weeks before treatment;
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 |
|---|---|---|
| R-CDOP+intrathecal MTXAlso: Pegylated liposome doxorubicin（PLD）R-CDOP+intrathecal MTX： * Rituximab 375 mg / m^2，D1 * Cyclophosphamide 750 mg / m^2，D2 * Doxorubicin Hydrochloride Liposome Injection 35mg / m^2，D2 * Vincristine 1.4mg/m^2 (dose capped at 2 mg)，D2 * Prednisone 50 mg， bid D2-6 * Cycle1-5：Intrathecal MTX 12 mg + DXM 5 mg after chemotherapy （PK patients will be given 24 h after chemotherapy） | Drug | R-CDOP+intrathecal MTX |
Primary outcome
2-year central nervous system relapse rate
Time frame: up to 6 years after the start of the study
The proportion of patients with central nervous system recurrence within two years from enrollment accounted for all patients treated with drugs.
Concentration of doxorubicin in cerebrospinal fluid after using doxorubicin hydrochloride liposome injection
Time frame: up to 4 years after the start of the study
CSF doxorubicin concentrations 24 hours after the first 5 courses of lipso-doxorubicin infusion will be tested. Peak concentration of doxorubicin in CSF will be recorded, and the area under the curve will be calculated.
10 secondary outcomes
Objective response rate (ORR)
Time frame: 2 years after enrollment of final patient
2-year progression-free survival (PFS) rate
Time frame: 2 years after enrollment of final patient
2-year event-free survival (EFS) rate
Time frame: 2 years after enrollment of final patient
Overall Survival (OS)
Time frame: 2 years after enrollment of final patient
Adverse events
Time frame: Since the signing of informed consent forms to 30 days after the last cycle
Cmax（maximum concentration）
Time frame: Time from zero to Tmax
Tmax（maximum time）
Time frame: Time from zero to Cmax
T1/2（drug half time）
Time frame: The time it takes for blood concentration levels to drop by half
AUC（0-∞）（area under the curve）
Time frame: Time from zero to ∞
AUC （0-t）（area under the curve from time zero to the last observation time
Time frame: Time from zero to the last observation time
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- 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.
Junning Cao, doctor contact
Dongmei Ji, doctor principal investigator
Fudan University
Junning Cao, Doctor principal investigator
Fudan University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing R-CDOP+intrathecal MTX in people with Diffuse Large B-cell Lymphoma, run by Fudan 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 15 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: looking for participants now, as of the sponsor's last update on 2 Apr 2026. 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dongmei Ji, doctor (13564183928, jidongmei2000@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-year central nervous system relapse rate (time frame: up to 6 years after the start of the study). The study lists 2 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 2 Apr 2026.