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

DLBCL Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03123718
• Other study ID #: HDMTX
• Status: Not yet recruiting
• Phase: Phase 3
• First received: April 18, 2017
• Last updated: April 21, 2017
• Start date: July 1, 2017
• Est. completion date: June 30, 2021

Study information

• Verified date: April 2017
• Source: Chonnam National University Hospital
• Contact: Deok-Hwan Yang
• Phone: +82-61-379-7636
• Email: drydh1685[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 205
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• DLBCL

Intervention

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.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeollanam-do

Sponsors (2)

Lead Sponsor	Collaborator
Chonnam National University Hospital	Consortium for Improving Survival of Lymphoma

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative incidence of CNS relapse	The rate of relapse will be analyzed by the cumulative incidence method	2 year
Secondary	Toxicity	Toxicity will be graded according to NCI-CTCAE v.4.03	2 year
Secondary	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.	2 year