DLBCLPhase 3NCT03123718
High-dose Intravenous Methotrexate Versus Intrathecal Methotrexate for Central Nervous System Prophylaxis in DLBCL
A Phase 3 study testing Intrathecal methotrexate and High-dose intravenous methotrexate in people with DLBCL, run by Chonnam National University Hospital at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- DLBCL
- What is being tested?
- Intrathecal methotrexate and High-dose intravenous methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 205 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Jul 2017to 30 Jun 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 21Show fewer
- 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),
- 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
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Chonnam National University Hwasun Hospital
Hwasun-gun, Jeollanam-do, 519-809
About this study
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
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
- Being tested
- Intrathecal methotrexate, High-dose intravenous methotrexate
- Keywords
- methotrexate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrathecal methotrexateDrug
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 methotrexateDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Intrathecal Methotrexate | Other | Not described Receives: Drug: Intrathecal methotrexate |
| High-dose Intravenous Methotrexate | Active comparator | Not described Receives: Drug: High-dose intravenous methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of CNS relapse
The rate of relapse will be analyzed by the cumulative incidence method
Measured: 2 year
Secondary outcomes (2)
Toxicity
Toxicity will be graded according to NCI-CTCAE v.4.03
Measured: 2 year
Progression-free survival (PFS)
PFS will be calculated from randomization to the date of CNS relapse and/or systemic disease progression, death, or last follow-up, as appropriate.
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2017
- Study start1 Jul 2017 (estimated)
- Primary completion30 Jun 2021 (estimated)
- Study completion30 Jun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DLBCLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 205 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chonnam National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Consortium for Improving Survival of Lymphoma
- Responsible party
- Principal investigator, Deok-Hwan Yang, Chonnam National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03123718
- Sponsor's protocol ID
- HDMTX
- Status last verified
- Apr 2017
- First submitted
- 18 Apr 2017
- Last updated
- 24 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03123718
- Acronym / sponsor ID
- HDMTX
- Conditions
- DLBCL
- Keywords
- methotrexate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 205 participants (estimated)
- Lead sponsor
- Chonnam National University HospitalUniversity, hospital or other
- Collaborators
- Consortium for Improving Survival of Lymphoma
- Study start
- 1 Jul 2017 (estimated)
- Primary completion
- 30 Jun 2021 (estimated)
- Study completion
- 30 Jun 2021 (estimated)
- First posted
- 21 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intrathecal Methotrexate | Other | Drug: Intrathecal methotrexate |
| High-dose Intravenous Methotrexate | Active comparator | Drug: High-dose intravenous methotrexate |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Aged ≥18 years <80
- Newly diagnosed, histologically confirmed DLBCL
- High-risk of CNS recurrence at diagnosis:
- Estimated life expectancy of more than 90 days
- Performance status (ECOG) ≤ 2
Key exclusion criteria (21 listed)
- Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol
- DLBCL or following subtypes:
- Previous immunochemotherapeutic treatment for DLBCL other than short-term use of corticosteroids (≤ 8 days before randomization)
- Previous radiotherapy
- CNS involvement of DLBCL at diagnosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrathecal methotrexateIntrathecal 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. | Drug | Intrathecal Methotrexate |
| High-dose intravenous methotrexateIntravenous 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. | Drug | High-dose Intravenous Methotrexate |
Primary outcome
Cumulative incidence of CNS relapse
Time frame: 2 year
The rate of relapse will be analyzed by the cumulative incidence method
2 secondary outcomes
Toxicity
Time frame: 2 year
Progression-free survival (PFS)
Time frame: 2 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intrathecal methotrexate and High-dose intravenous methotrexate in people with DLBCL, run by Chonnam National University Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Deok-Hwan Yang (+82-61-379-7636, drydh1685@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative incidence of CNS relapse (time frame: 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2017.