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

April 21, 2017 updated by: Deok-Hwan Yang, Chonnam National University Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
205

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Korea, Republic of
    • Jeollanam-do
      • Hwasun-gun, Jeollanam-do, Korea, Republic of, 519-809
        • Chonnam National University Hwasun Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cumulative incidence of CNS relapse
Time Frame: 2 year
The rate of relapse will be analyzed by the cumulative incidence method
2 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Toxicity
Time Frame: 2 year
Toxicity will be graded according to NCI-CTCAE v.4.03
2 year
Progression-free survival (PFS)
Time Frame: 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.
2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chonnam National University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Consortium for Improving Survival of Lymphoma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 24, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HDMTX

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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