High-dose Intravenous Methotrexate Versus Intrathecal Methotrexate for Central Nervous System Prophylaxis in DLBCL
Prospective, Multicenter, Randomized ,Open-labeled, Phase III Study Comparing High-dose Intravenous Methotrexate Versus Intrathecal Methotrexate for the Prophylaxis of Central Nervous System Relapse in Diffuse Large B Cell Lymphoma
1 other identifier
interventional
205
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jul 2017
Typical duration for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 18, 2017
CompletedFirst Posted
Study publicly available on registry
April 21, 2017
CompletedStudy Start
First participant enrolled
July 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2021
CompletedApril 24, 2017
April 1, 2017
4 years
April 18, 2017
April 21, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Cumulative incidence of CNS relapse
The rate of relapse will be analyzed by the cumulative incidence method
2 year
Secondary Outcomes (2)
Toxicity
2 year
Progression-free survival (PFS)
2 year
Study Arms (2)
Intrathecal Methotrexate
OTHERHigh-dose Intravenous Methotrexate
ACTIVE COMPARATORInterventions
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.
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.
Eligibility Criteria
You may qualify if:
- Aged ≥18 years \<80
- Newly diagnosed, histologically confirmed DLBCL
- High-risk of CNS recurrence at diagnosis:
- Age-adjusted IPI (aaIPI) ≥2 or IPI ≥4 with extranodal involvement of \>1 site plus serum lactate dehydrogenase (LDH) \> normal OR
- 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
You may not qualify if:
- Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol
- DLBCL or following subtypes:
- Primary mediastinal large B-cell lymphoma
- Grey zone lymphoma)
- 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
- Absolute neutrophil count \< 1,500 cells/mm3 (1.5 x 109/L),
- Platelet count \< 100,000/mm3 (100 x 109/L), or \< 75,000 /mm3 in patients with bone marrow involvement,
- Serum aspartate transaminase or serum alanine transaminase ≥3.0 x upper limit of normal (ULN),
- Serum total bilirubin \> 2 x ULN (with the exception of hemolytic anemia),
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Chonnam National University Hwasun Hospital
Hwasun-gun, Jeollanam-do, 519-809, South Korea
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 18, 2017
First Posted
April 21, 2017
Study Start
July 1, 2017
Primary Completion
June 30, 2021
Study Completion
June 30, 2021
Last Updated
April 24, 2017
Record last verified: 2017-04
Data Sharing
- IPD Sharing
- Will not share