RecruitingPhase 2NCT05257018

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

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

Sponsor

Fudan University

Enrollment

83 participants

Start Date

Feb 26, 2022

Study Type

INTERVENTIONAL

Conditions

Diffuse Large B Cell Lymphoma

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

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria15

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;

Exclusion Criteria15

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;

Interventions

DRUGR-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）