Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
septembre 2022
juillet 2025
18 septembre 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | HOUILLIER Caroline | 18/09/2025 17:32:04 | Contacter | ||
| AP-HP Assistance publique - Hôpitaux de Paris | 18/09/2025 17:32:04 | Contacter | |||
| AP-HP - Hôpital La Pitié-Salpêtrière | |||||
| AP-HP - Hôpital Lariboisiere-Fernand Widal | |||||
| AP-HP - Hôpital Saint Louis | |||||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| 18/09/2025 17:32:03 | Contact (sur clinicalTrials) | ||||
| 18/09/2025 17:32:03 | Contact (sur clinicalTrials) | ||||
| 18/09/2025 17:32:04 | Contact (sur clinicalTrials) | ||||
| 18/09/2025 17:32:04 | Contact (sur clinicalTrials) | ||||
| 18/09/2025 17:32:04 | Contact (sur clinicalTrials) | ||||
| 18/09/2025 17:32:04 | Contact (sur clinicalTrials) | ||||
| 18/09/2025 17:32:04 | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Hôpital Pitié-Salpêtrière - 75013 - Paris - France | Caroline HOUILLIER, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
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
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
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.