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

NCT ID: NCT05257018

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-26
• Study Completion Date: 2028-01-30

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R-CDOP+intrathecal MTX

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）

Group Type: EXPERIMENTAL

R-CDOP+intrathecal MTX

Intervention Type: 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）

Interventions

R-CDOP+intrathecal MTX

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）

Intervention Type: DRUG

Other Intervention Names

Pegylated liposome doxorubicin（PLD）

Eligibility Criteria

Inclusion Criteria

1. Age range from 18 to 75 years;

2. ECOG performance status: 0-2;

3. 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:

1. CNS-IPI 4-6;

2. 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;

3. PCLBCL-leg;

4. 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;

5. 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;

6. Liver function: total bilirubin, ALT, AST < 1.5×UNL (upper limit of normal);

7. Renal function: Cr < 1.5×UNL and creatinine clearance≥30 ml/min;

8. Echocardiography or nuclide cardiac function testing with LVEF≥50%;

9. 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;

10. Consent to provide pathological tissue specimens (wax blocks within half a year or 20 slides for paraffin tissue sections);

11. Life expectancy≥3 months;

12. Signed informed consent;

Exclusion Criteria

1. Patients with a known history of severe allergy to humanized or murine mAbs, or any contraindication to R-CDOP, intrathecal MTX;

2. Patients with evidence of CNS involvement (baseline cerebrospinal fluid, imaging, symptoms);

3. 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;

4. 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;

5. Those who had a second degree or greater operation within three weeks before treatment;

6. Diagnosed with a malignancy other than lymphoma or under treatment, with the following exceptions:

1. Had received treatment with curative intent and had not developed malignancy with known active disease ≥ 5 years prior to enrollment;

2. Basal cell carcinoma of the skin (other than melanoma) that has been adequately treated with no evidence of disease;

3. Carcinoma in situ of the cervix that has been adequately treated with no evidence of disease;

7. Had significant coagulation abnormalities;

8. Any previous antilymphoma therapy other than short-term corticosteroids (up to 10 days);

9. Those with severe active infection;

10. 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;

11. 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;

12. Pregnant or lactating women;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Ji Dongmei

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dongmei Ji, doctor

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Junning Cao, Doctor

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Dongmei Ji

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Cancer Hospital affilicaited to Xinjiang Medical University

Ürümqi, Xinjiang, China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Dongmei Ji, doctor

Role: CONTACT

jidongmei2000@126.com

13564183928

Junning Cao, doctor

Role: CONTACT

cao_junning@126.com

Facility Contacts

dongmei ji, doctor

Role: primary

dongmei ji

Role: backup

jidongmei2000@126.com

13564183928

Shujuan Wen, Doctor

Role: primary

Other Identifiers

CSPC-DMS-LM-K001

Identifier Type: -

Identifier Source: org_study_id