Clinical trial · Interventional
Dose Dense Re-challenge of High Dose Methotrexate With Glucarpidase for Relapsed Primary Central Nervous System Lymphoma
Dose Dense Re-challenge of High Dose Methotrexate (HD-MTX) With Glucarpidase (CPG2) for Relapsed Primary Central Nervous System Lymphoma (PCNSL): A Phase I Trial
NCT05135858CI-TRIAL-00061675METHOGLUunknownPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
High dose intravenous Methotrexate (HD-MTX) is the key drug in the treatment of primary central nervous system lymphoma (PCNSL). HD-MTX is usually delivered with time interval ranging from 10 to 21 days. Reduction of injection time interval is limited by MTX renal excretion and systemic toxicity. Glucarpidase (CPG2) is a recombinant bacterial rescue enzyme that cleaves circulating MTX into inactive metabolites, reducing plasma MTX concentrations within few minutes. The research hypothesis is that CPG2 used after HD-MTX injection allows to reduce time interval between MTX injections, increase dose intensity of the chemotherapy, reduce systemic toxicity and duration of hospitalization.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Primary Central Nervous System Lymphoma | Primary Central Nervous System Lymphoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Glucarpidase | Drug | — | UNRESOLVED |
| Methotrexate (MTX) | Drug | Methotrexate | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- CPG2
- description
- 6 infusions of glucarpidase
- interventionNames
- Drug: Glucarpidase
- Drug: Methotrexate (MTX)
Primary outcomes (1)
- measure
- The occurrence of a dose schedule limiting toxicity (DLT)
- timeFrame
- 25th day after the first injection of methotrexate
- description
- defined as any of the following events assessed as related or possibly related to methotrexate: * Any grade V toxicity (according to NCI-CTCAE v 5.0) * Grade IV non-haematological toxicity excluding fatigue, alopecia, nausea, vomiting (according to NCI-CTCAE v 5.0) * Creatinine \> 3 X baseline (grade III toxicity according to NCI-CTCAE v 5.0) * Grade IV thrombopenia, grade III thrombopenia with bleeding, grade IV neutropenia or grade III neutropenia with fever,lasting \> 3 days (according to NCI-CTCAE v 5.0) * Delay in MTX administration \> 36 hours due to any adverse effect.
Secondary outcomes (10)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: 1. Cerebral relapse of primary CNS lymphoma (any line) 2. Pathological diagnosis of diffuse large B cell lymphoma (or cytological diagnosis in the CSF or in the vitreous) at initial diagnosis (not mandatory at the time of the present relapse) 3. Absence of any systemic involvement confirmed by full body CT scan and/or FDG-PET scan 4. Age≥18 years 5. HD-MTX based chemotherapy in first line treatment, with complete response lasting at least 6 months after the end of the 1st line treatment 6. No administration of other anticancer therapy within the 3 weeks prior to inclusion 7. Karnofsky performance status (KPS) ≥ 50 8. Adequate haematological, renal and hepatic function (adequate Laboratory Parameters within 21 days): 1. Absolute neutrophil count (ANC) \>1000/mm3 2. Platelets \> 100,000/mm3 independent of transfusion support 3. Alanine aminotransferase and aspartate aminotransferase ≤ 3 x upper limit of normal (ULN) and/or total bilirubin ≤ 1,5x ULN, unless related to Gilbert's or Meulengracht disease 4. Estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73m2) (MDRD) 9. All non-hematological adverse events (AEs) related to prior therapy completely resolved or improved to Grade 1-2 (except for alopecia or fatigue). 10. Written informed consent, which could be signed by the trustworthy person or close relatives in case the neurologic status of the patient does not allow him to sign. In case the patient is unable to sign the consent at baseline, but his neurological status improves during the treatment, he will be asked to give his written informed "follow-up" consent Exclusion Criteria: 1. Positive HIV serology 2. Active viral infection with Hepatitis B or C virus 3. Preexisting immunodeficiency (organ transplant recipient) 4. Relevant congestive heart failure interfering with hydration 5. Isolated CNS relapse of systemic non-Hodgkin's lymphoma (NHL) 6. Pregnancy or lactation. An effective contraception is mandatory for patients (men and women of childbearing potential) all along the study participation and during at least 6 months after the end of MTX. Men must not donate sperm all along the study participation and during at least 6 months after the end of MTX. 7. Third space (i.e. pleural effusion, ascites, extended oedema). 8. Obesity (body mass index \>30 kg/m2). 9. Any other active malignancy, except basocellular carcinoma and non-invasive cervix cancer 10. Absolute contraindication to MTX or leucovorin 11. Previous use of carboxypeptidase for delayed MTX excretion and kidney dysfunction after HD-MTX 12. No social security affiliation 13. Persons under legal protection (tutorship or curatorship) or safety measure 14. Participation in any other clinical trial (Jardé 1 and 2) either 1 month prior to or during this study.
References
Publications (0)
Data not yet available
No reference posted for this study.