High-dose Intravenous Methotrexate Versus Intrathecal Methotrexate for Central Nervous System Prophylaxis in DLBCL

NCT ID: NCT03123718

Last Updated: 2017-04-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 205 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2021-06-30

Brief Summary

The outcome of patients with central nervous system (CNS) relapse in DLBCL is poor, with median survival times of 2-5 months. This fatal prognosis necessitates CNS prevention in a subgroup of patients with a high risk of CNS relapse.

Intrathecal methotrexate (ITMTX) has traditionally been used, although its efficacy for CNS prophylaxis is contradictory. High-dose intravenous methotrexate (IVMTX) has been suggested as an alternative approach. Considering the lack of evidence supporting the role of ITMTX, the investigators propose to compare the efficacy of ITMTX and IVMTX for prophylaxis of CNS relapse in a subgroup of patients with DLBCL at a high risk for CNS relapse.

Conditions

DLBCL

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Intrathecal Methotrexate

Group Type: OTHER

Intrathecal methotrexate

Intervention Type: DRUG

Intrathecal administration of 2nd, 3rd, and 4th doses of methotrexate 15 mg and hydrocortisone 50mg on day 2 or 3 of 2nd, 3rd, and 4th cycles of immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP), respectively.

High-dose Intravenous Methotrexate

Group Type: ACTIVE_COMPARATOR

High-dose intravenous methotrexate

Intervention Type: DRUG

Intravenous administration of 1st and 2nd doses of methotrexate 3g/m2 on day 15 of 2nd and 6th cycles of immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP), respectively.

• Dose of intravenous methotrexate will be reduced to 2g/m2 for patients aged >70 years.

Interventions

Intrathecal methotrexate

Intrathecal administration of 2nd, 3rd, and 4th doses of methotrexate 15 mg and hydrocortisone 50mg on day 2 or 3 of 2nd, 3rd, and 4th cycles of immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP), respectively.

Intervention Type: DRUG

High-dose intravenous methotrexate

Intravenous administration of 1st and 2nd doses of methotrexate 3g/m2 on day 15 of 2nd and 6th cycles of immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP), respectively.

• Dose of intravenous methotrexate will be reduced to 2g/m2 for patients aged >70 years.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged ≥18 years <80
• Newly diagnosed, histologically confirmed DLBCL
• High-risk of CNS recurrence at diagnosis:

1. Age-adjusted IPI (aaIPI) ≥2 or IPI ≥4 with extranodal involvement of >1 site plus serum lactate dehydrogenase (LDH) > normal OR

2. Involvement of high-risk locations: bone marrow, nasal or paranasal sinuses, testis, epidural disease (paravertebral or vertebra), breast, adrenal or kidney

• Estimated life expectancy of more than 90 days
• Performance status (ECOG) ≤ 2
• Written informed consent

Exclusion Criteria

• Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol
• DLBCL or following subtypes:

1. Primary mediastinal large B-cell lymphoma

2. Grey zone lymphoma)

3. Primary cutaneous DLBCL

• Previous immunochemotherapeutic treatment for DLBCL other than short-term use of corticosteroids (≤ 8 days before randomization)
• Previous radiotherapy
• CNS involvement of DLBCL at diagnosis
• HIV positive
• Any contraindication for application of RCHOP or high dose methotrexate
• Any of following laboratory results

1. Absolute neutrophil count < 1,500 cells/mm3 (1.5 x 109/L),

2. Platelet count < 100,000/mm3 (100 x 109/L), or < 75,000 /mm3 in patients with bone marrow involvement,

3. Serum aspartate transaminase or serum alanine transaminase ≥3.0 x upper limit of normal (ULN),

4. Serum total bilirubin > 2 x ULN (with the exception of hemolytic anemia),

• Serum creatinine >2.0 x ULN or creatinine clearance <50 mL/min
• Active cancer except curable basal cell carcinoma, cervical cancer in situ, and/or papillary thyroid cancer during the last five years
• Ejection fraction < 45% on echocardiography
• Uncontrolled active hepatitis
• Pregnancy or breast-feeding
• Men and women of reproductive potential no agreeing to use an acceptable method of birth control during treatment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Consortium for Improving Survival of Lymphoma

OTHER

Sponsor Role: collaborator

Chonnam National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Deok-Hwan Yang

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, South Korea

Countries

South Korea

Central Contacts

Deok-Hwan Yang

Role: CONTACT

drydh1685@hotmail.com

+82-61-379-7636

Seung-Ah Yahng

Role: CONTACT

saymd@catholic.ac.kr

+82-32-280-5893

Other Identifiers

HDMTX

Identifier Type: -

Identifier Source: org_study_id