Combining R-CDOP and intrathecal methotrexate for high-risk DLBCL patients

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 study is testing a new combination of chemotherapy and a specific type of treatment for high-risk patients with untreated diffuse large B-cell lymphoma to see if it helps prevent serious complications in the brain.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 83 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: methotrexate, rituximab, chemotherapy, cyclophosphamide, doxorubicin, prednisone
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT05257018 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial evaluates the safety and efficacy of the R-CDOP regimen combined with intrathecal methotrexate in patients with untreated diffuse large B-cell lymphoma (DLBCL) who are at high risk for central nervous system (CNS) relapse. The study involves administering 6-8 cycles of chemotherapy every three weeks, with intrathecal methotrexate given after the first five cycles. Patients will undergo a mid-treatment PET scan after four cycles to assess their response, with treatment adjustments based on their response status. The trial aims to improve outcomes for patients who are at significant risk of CNS involvement, which is often fatal.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with untreated diffuse large B-cell lymphoma and specific high-risk features for CNS relapse.

Not a fit: Patients with low-risk DLBCL or those who have received prior treatment for their lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the risk of CNS relapse in high-risk DLBCL patients, potentially improving survival rates.

How similar studies have performed: While the standard R-CHOP regimen is well-established, this specific combination approach is novel and has not been extensively tested in prior studies.

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;

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• Dongmei Ji — Shanghai, Shanghai Municipality, China (Recruiting)
• Cancer Hospital affilicaited to Xinjiang Medical University — Ürümqi, Xinjiang, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Dongmei Ji, doctor — Fudan University
• Study coordinator: Dongmei Ji, doctor

Conditions Diffuse Large B-cell Lymphoma; Chemo-naive Diffuse Large B-cell Lymphoma; Doxorubicin Hydrochloride Liposome Injection; Methotrexate; Central Nervous System Relapsed; R-CDOP; Objective Response Rate; Progression Free Survival