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

Sponsor
Chonnam National University Hospital (Other)
Overall Status
Unknown status
CT.gov ID
NCT03123718
Collaborator
Consortium for Improving Survival of Lymphoma (Other)
205
1
2
48
4.3

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Intrathecal methotrexate
  • Drug: High-dose intravenous methotrexate
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
205 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
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
Anticipated Study Start Date :
Jul 1, 2017
Anticipated Primary Completion Date :
Jun 30, 2021
Anticipated Study Completion Date :
Jun 30, 2021

Arms and Interventions

Arm Intervention/Treatment
Other: Intrathecal Methotrexate

Drug: 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.

Active Comparator: High-dose Intravenous Methotrexate

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.

Outcome Measures

Primary Outcome Measures

  1. Cumulative incidence of CNS relapse [2 year]

    The rate of relapse will be analyzed by the cumulative incidence method

Secondary Outcome Measures

  1. Toxicity [2 year]

    Toxicity will be graded according to NCI-CTCAE v.4.03

  2. Progression-free survival (PFS) [2 year]

    PFS will be calculated from randomization to the date of CNS relapse and/or systemic disease progression, death, or last follow-up, as appropriate.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Chonnam National University Hwasun Hospital Hwasun-gun Jeollanam-do Korea, Republic of 519-809

Sponsors and Collaborators

  • Chonnam National University Hospital
  • Consortium for Improving Survival of Lymphoma

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Deok-Hwan Yang, Principal Investigator, Chonnam National University Hospital
ClinicalTrials.gov Identifier:
NCT03123718
Other Study ID Numbers:
  • HDMTX
First Posted:
Apr 21, 2017
Last Update Posted:
Apr 24, 2017
Last Verified:
Apr 1, 2017
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Deok-Hwan Yang, Principal Investigator, Chonnam National University Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 24, 2017