Reduction of MTX Levels After Glucarpidase Treatment in DLBCL Patients at Risk of CNS

NCT05022797 | Terminated Phase 2

• 2 other identifiers: MDA-BTG-2020-012020-004450-30
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

Diffuse large B-cell lymphoma (DLBCL) is an aggressive subset of non-Hodgkin's lymphoma (NHL). Central nervous system (CNS) involvement in patients with NHL is a serious complication. The outcome of patients with CNS relapse is extremely poor, with a median survival of 4-6 months. One approach to reduce CNS relapse in high-risk patients is the use of systemic high-dose intravenous (iv) methotrexate (HMTX) chemotherapy. Currently available methods of MTX clearance, including dialysis-based methods, have shown limited efficacy. Glucarpidase hydrolyses MTX to inactive metabolites that are partially metabolised by the liver, thus providing an alternative route of limiting renal excretion. The administration of Glucarpidase could prevent MTX toxicity as a whole as well as the following consequences. The aim of this study is to analyse the prophylactic effect of 2,000 units of glucarpidase administered after 12 hours of HDMTX on MTX clearance and on the incidence and severity of MTX-related toxicity.

Conditions

Diffuse Large B-Cell Lymphoma; Drug Toxicity

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who achieve significant change blood MTX levels (more than 95% reduction of blood MTX levels) at 6 hours after administration of Glucarpidase

  As a categorical variable: \>95% reduction of MTX (yes/no) after 6 hours after administration of 2,000 units of Glucarpidase.

  6 hours

Secondary Outcomes (3)

• Change blood MTX levels achieved at 15 minutes, 6 hours, 12 hours and 24 hours after administration of Glucarpidase

  15min, 6 hours, 12 hours, 24 hours

• Proportion of patients with more than 95% reduction of blood MTX levels after administration of Glucarpidase

  15min, 6 hours, 12 hours, 24 hours

• Proportion of patients who achieve clinically important reduction (CIR) in blood MTX level at 15 minutes, 6 hours, 12 hours and 24 hours after administration of Glucarpidase.

  15min, 6 hours, 12 hours, 24 hours

Study Arms (1)

Glucarpidase, methotrexate, R-CHOP

EXPERIMENTAL

Glucarpidase 2000Units per dose. IV. Bolus injection over 5 minutes. Administered 12 hours following after each HDMTX cycle, for a maximum of 3 cycles.

Drug: Glucarpidase 1000 UNT [Voraxaze]

Interventions

Glucarpidase 1000 UNT [Voraxaze] DRUG

2 vials of 1000 units per vial

Also known as: VORAXAZE®, P21011D

Glucarpidase, methotrexate, R-CHOP

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged 18-70 years
• Patients with diagnosis of diffuse large B-cell lymphoma
• Patients at high risk of CNS involvement (\>2 extranodal sites plus an elevated LDH or /and involvement of high-risk extranodal sites including testes, paranasal sinuses, breast, liver, adrenal and renal)
• Patients who will receive HDMTX (three cycles) into R-CHOP regimen (6 cycles) prescribed according to normal clinical practice
• Absence of focal neurological signs
• Absence of CNS involvement determined by cerebrospinal fluid (CSF) cytometry flow test prior to start treatment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count 1800-7500/µL, platelet count 130.000- 450.000/ µL, hemoglobin 13,5-18 g/dL,
• Serum creatinine ≤1.5 x the upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥60ml/min/1.73m\^2
• Total serum bilirubin ≤2 x ULN. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5 x ULN
• Ability to understand and the willingness to sign a written informed consent document
• In women of childbearing potential (from menarche and until becoming post-menopausal \[i.e., no menses for 12 months with an alternative medical cause\], unless permanently sterile) and men, use of highly effective measure of contraception (abstinence, hormonal contraception, intra-uterine device \[IUD\], intrauterine hormone-releasing system, \[IUS\], or anatomical sterility in self or partner) committed during 3 months after the last IMP administration.

You may not qualify if:

• Patients suffered from cardiovascular diseases (arrhythmias, previous heart failure, thromboembolic disease)
• Previous treatment with Glucarpidase
• Pregnant or breastfeeding women
• Concomitant treatment with agents which interact with methotrexate metabolism or excretion
• Known intolerance/hypersensitivity to Glucarpidase or any of its excipients.

Sponsors & Collaborators

• Fundacion CRIS de Investigación para Vencer el Cáncer: lead
• BioClever 2005 S.L.: collaborator
• Eurofins ADME, S.L.: collaborator
• NTShub, S.L.: collaborator
• BTG International Inc.: collaborator

Study Sites (2)

MD Anderson

Madrid, 28033, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Drug-Related Side Effects and Adverse Reactions

Interventions

glucarpidase

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chemically-Induced Disorders

Study Officials

• Adolfo De la Fuente, PD

  MD Anderson

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 26, 2021
• Study Start: July 19, 2021
• Primary Completion: November 22, 2022
• Study Completion: November 22, 2022
• Last Updated: May 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)