R-CDOP Combined With Intrathecal Methotrexate for DLBCL Patients With High-risk of CNS Relapse

NCT05257018 | Recruiting Phase 2

• 1 other identifier: CSPC-DMS-LM-K001
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 2

Brief 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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  up to 4 years after the start of the study

Secondary Outcomes (10)

• Objective response rate (ORR)

  2 years after enrollment of final patient

• 2-year progression-free survival (PFS) rate

  2 years after enrollment of final patient

• 2-year event-free survival (EFS) rate

  2 years after enrollment of final patient

• Overall Survival (OS)

  2 years after enrollment of final patient

• Adverse events

  Since the signing of informed consent forms to 30 days after the last cycle

Study Arms (1)

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）

Drug: R-CDOP+intrathecal MTX

Interventions

R-CDOP+intrathecal MTX DRUG

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）

Also known as: Pegylated liposome doxorubicin（PLD）

R-CDOP+intrathecal MTX

Eligibility Criteria

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

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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:
• 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;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (2)

Dongmei Ji

Shanghai, Shanghai Municipality, 021, China

RECRUITING

Cancer Hospital affilicaited to Xinjiang Medical University

Ürümqi, Xinjiang, China

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Dongmei Ji, doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

• Junning Cao, Doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dongmei Ji, doctor

CONTACT

13564183928; jidongmei2000@126.com

Junning Cao, doctor

CONTACT

cao_junning@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: February 25, 2022
• Study Start: February 26, 2022
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)