Reduction of MTX Levels After Glucarpidase Treatment in DLBCL Patients at Risk of CNS
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|ClinicalTrials.gov Identifier: NCT05022797|
Recruitment Status : Recruiting
First Posted : August 26, 2021
Last Update Posted : September 8, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-Cell Lymphoma Drug Toxicity||Drug: Glucarpidase 1000 UNT [Voraxaze]||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Reduction of MTX Levels After Treatment With Reduced Glucarpidase Dose in Patients With DLBCL at Risk of CNS Involvement Who Receive Cycles of HDMTX: an Open-label, Interventional, Non-randomized, Phase 2, Pilot, Multicenter Study|
|Actual Study Start Date :||July 19, 2021|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||December 2023|
Experimental: Glucarpidase, methotrexate, R-CHOP
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]
2 vials of 1000 units per vial
Other Name: VORAXAZE®, P21011D
- 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 [ Time Frame: 6 hours ]As a categorical variable: >95% reduction of MTX (yes/no) after 6 hours after administration of 2,000 units of Glucarpidase.
- Change blood MTX levels achieved at 15 minutes, 6 hours, 12 hours and 24 hours after administration of Glucarpidase [ Time Frame: 15min, 6 hours, 12 hours, 24 hours ]As a numerical variable: MTX in µmol/L before and after 15 minutes, 6 hours, 12 hours and 24 hours after administration of 2,000 units of Glucarpidase.
- Proportion of patients with more than 95% reduction of blood MTX levels after administration of Glucarpidase [ Time Frame: 15min, 6 hours, 12 hours, 24 hours ]As a numerical variable: MTX change from baseline in µmol/L after 15 minutes, 6 hours, 12 hours and 24 hours after administration of 2,000 units of Glucarpidase.
- 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. [ Time Frame: 15min, 6 hours, 12 hours, 24 hours ]CIR is defined as a reduction in blood MTX concentration to ≤ 1 µmol/L in post-Glucarpidase time points. As a categorical variable: reduction in blood MTX concentration to ≤ 1 µmol/L (yes/no) after 15 minutes, 6 hours, 12 hours and 24 hours after administration of 2,000 units of Glucarpidase.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05022797
|Contact: Tamara Mondéjar, PD||+34 firstname.lastname@example.org|
|Contact: Antonio López, PD||+34 609 114 email@example.com|
|Madrid, Spain, 28033|
|Contact: Adolfo De la Fuente, PD +34 912 77 72 20 firstname.lastname@example.org|
|Principal Investigator: Adolfo De la Funete, PD|
|Sub-Investigator: Raquel Oña|
|Sub-Investigator: Mónica Estévez|
|Sub-Investigator: Rebeca Iglesias|
|Hospital Universitario Ramón y Cajal||Active, not recruiting|
|Madrid, Spain, 28034|
|Principal Investigator:||Adolfo De la Fuente, PD||MD Anderson|