JCOG2201: A randomized phase III study of pola-R-CHP/High-dose methotrexate/IT vs. Pola-R-CHP/IT for diffuse large B-cell lymphoma with high risk of CNS relapse

JRCT ID: jRCTs031230505

Registered date:12/12/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Untreated diffuse large B-cell lymphoma with high risk of CNS relapse
• Date of first enrollment: 12/12/2023
• Target sample size: 390
• Study type: Interventional

Intervention(s)

Arm A: Pola-R-CHOP (polatuzumab vedotin 1.8 mg/kg div day 1, rituximab 375 mg/m2 div day 1, cyclophosphamide 750 mg/m2 div day 1, doxorubicin 50 mg/m2 div day 1, prednisolone 100 mg/body [40 mg/m2 for those 65 years and older] po day 1-5, and G-CSF sc day 2-) is administered 6 courses followed by 2 courses of rituximab (rituximab 375 mg/m2 div day 1). Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) is administered 4 times during the pola-R-CHOP phase.
Patients with testicular disease who achieve complete response after chemotherapy receive testicular radiotherapy (30 Gy/15 Fr).

Arm B: Pola-R-CHOP is administered 3 courses followed by 2 courses of R-HDMTX (rituximab 375 mg/m2 div day 1, methotrexate 3.5 g/m2 div day 2, and leucovorin 24 mg div 4 times daily day 3-5) and 3 additional courses of pola-R-CHOP. Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) is administered 4 times during the pola-R-CHOP phase.
Patients with testicular disease who achieve complete response after chemotherapy receive testicular radiotherapy (30 Gy/15 Fr).

Outcome(s)

• Primary Outcome: Progression-free survival
• Secondary Outcome: Overall survival, cumurative incidence of CNS, response rate, complete response rate, adverse events, serious adverse events.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 79age old
• Gender: Both

Include criteria

(1) Pathologically proven mature B-cell neoplasms of the following except for histological transformation from lymphoid tumors other than diffuse large B-cell lymphoma (DLBCL).
DLBCL, NOS
T-cell/histiocyte-rich large B-cell lymphoma
Primary cutaneous DLCBL, leg type
EBV positive DLCBL, NOS
ALK-positive large B-cell lymphoma
(2) No diagnosis of high-grade B-cell lymphoma when FISH or chromosome testing is performed. If treatment needs to be started immediately, the patient may be registered before the test results are confirmed.
(3) CD20 positive.
(4) Any of the following (i) to (iii) are fulfilled.
(i) CNS-IPI score of 4 to 6
(ii) CNS-IPI score of 0 to 3 with involvement of one or more of the organs at high risk of CNS relapse
(iii) CNS-IPI score of 0 to 3 with no lesions of the organs at high risk of CNS relapse and 3 or more extranodal lesions.
(5) Aged 18 to 79 years old
(6) ECOG performance status (PS) of 0 to 2
(7) The presence or absence of measurable lesions is not required
(8) No central nervous system involvement
(9) No prior chemotherapy, radiotherapy, interferon-alfa, or antibody therapy for DLBCL
(10) No prior immunosuppressant treatment.
(11) Sufficient organ function (assessed whithin 14 days prior to registration):
(i) Peripheral blood tumor cell count>= 10,000/mm3
(ii) Absolute neutrophil count >= 1,000/mm3
(iii) Platelet count >= 75,000/mm3 (>= 50,000/mm3 in patients with bone marrow invasion of lymphoma)
(iv) Total bilirubin <= 2.0 mg/dL
(v) AST <=100 U/L
(vi) ALT <= 100 U/L
(vii) Serum creatinine <= 1.5 mg/dL
(vii) SpO2 >= 93% (room air)
(12) No ischemic change, atrial fibrillation, or ventricular arrhythmias requiring treatment on the latest ECG (assessed whithin 28 days prior to registration)
(13) Left ventricular ejection fraction >= 50% (assessed whithin 56 days prior to registration)
(14) Written informed consent

Exclude criteria

(1) Synchronous double or multiple cancer or metachronous double or multiple cancer with progression free period less than 5 years.
(2) Infectious disease requiring systemic treatment.
(3) A fever over 38 degrees (except when infection or drug fever can be ruled out).
(4) Female during pregnancy, within 28 days of postparturition, or during lactation and male expecting partner's pregnancy.
(5) Severe psychological disorder.
(6) Receiving continuous systemic corticosteroid or immunosuppressant treatment.
(7) Uncontrollable diabetes mellitus.
(8) Uncontrollable hypertension.
(9) Unstable angina pectoris, or history of myocardial infarction within 6 months.
(10) Uncontrollable valvular heart disease, dilated cardiomyopathy, or hypertrophic cardiomyopathy.
(11) Positive HBs antigen or HCV antibody.
(12) Positive HIV antibody.
(13) Interstitial pneumonia, pulmonary fibrosis or severe pulmonary emphysema on chest X-ray.

Related Information

• Primary Sponsor: YAMAGUCHI Motoko
• Source(s) of Monetary Support: National Cancer Center Japan