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

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.

Eligibility

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;

Conditions2

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