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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
Sponsor:
Collaborators:
BioClever 2005 S.L.
Eurofins ADME, S.L.
NTShub, S.L.
BTG International Inc.
Information provided by (Responsible Party):
Fundacion CRIS de Investigación para Vencer el Cáncer

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.


Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Drug Toxicity Drug: Glucarpidase 1000 UNT [Voraxaze] Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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




Primary Outcome Measures :
  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 [ 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects aged 18-70 years
  2. Patients with diagnosis of diffuse large B-cell lymphoma
  3. 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)
  4. Patients who will receive HDMTX (three cycles) into R-CHOP regimen (6 cycles) prescribed according to normal clinical practice
  5. Absence of focal neurological signs
  6. Absence of CNS involvement determined by cerebrospinal fluid (CSF) cytometry flow test prior to start treatment
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  8. Absolute neutrophil count 1800-7500/µL, platelet count 130.000- 450.000/ µL, hemoglobin 13,5-18 g/dL,
  9. Serum creatinine ≤1.5 x the upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥60ml/min/1.73m^2
  10. Total serum bilirubin ≤2 x ULN. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5 x ULN
  11. Ability to understand and the willingness to sign a written informed consent document
  12. 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.

Exclusion Criteria:

  1. Malignant disease, other than those being treated in this study. Exceptions to this exclusion include malignancies that were treated curatively and have not recurred within 2 years after completion of treatment.
  2. Patients suffered from cardiovascular diseases (arrhythmias, previous heart failure, thromboembolic disease)
  3. Previous treatment with Glucarpidase
  4. Pregnant or breastfeeding women
  5. Concomitant treatment with agents which interact with methotrexate metabolism or excretion
  6. Known intolerance/hypersensitivity to Glucarpidase or any of its excipients.

Information from the National Library of Medicine

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


Contacts
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Contact: Tamara Mondéjar, PD +34 636258222 tmondejar@criscancer.org
Contact: Antonio López, PD +34 609 114 774 alopez@criscancer.org

Locations
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Spain
MD Anderson Recruiting
Madrid, Spain, 28033
Contact: Adolfo De la Fuente, PD    +34 912 77 72 20    afuente@mdanderson.es   
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
Sponsors and Collaborators
Fundacion CRIS de Investigación para Vencer el Cáncer
BioClever 2005 S.L.
Eurofins ADME, S.L.
NTShub, S.L.
BTG International Inc.
Investigators
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Principal Investigator: Adolfo De la Fuente, PD MD Anderson
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Responsible Party: Fundacion CRIS de Investigación para Vencer el Cáncer
ClinicalTrials.gov Identifier: NCT05022797    
Other Study ID Numbers: MDA-BTG-2020-01
2020-004450-30 ( EudraCT Number )
First Posted: August 26, 2021    Key Record Dates
Last Update Posted: September 8, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma, Large B-Cell, Diffuse
Drug-Related Side Effects and Adverse Reactions
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Chemically-Induced Disorders