Using glucarpidase to enhance methotrexate treatment for relapsed brain 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
This study is testing if adding glucarpidase to high-dose methotrexate can help people with relapsed brain lymphoma get better treatment while reducing side effects and hospital time.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Drugs / interventions | chemotherapy, Methotrexate |
| Locations | 1 site (Paris) |
| Trial ID | NCT05135858 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the use of glucarpidase in conjunction with high-dose methotrexate (HD-MTX) to treat relapsed primary central nervous system lymphoma. The study employs a Phase I, open-label, multicenter design with a 3+3 dose escalation approach to determine the minimum tolerated time interval between HD-MTX injections. Participants will receive fixed doses of HD-MTX followed by glucarpidase at varying intervals to assess safety and efficacy. The goal is to increase chemotherapy intensity while minimizing toxicity and hospital stay.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of cerebral relapse of primary CNS lymphoma who have previously responded to HD-MTX treatment.
Not a fit: Patients with systemic involvement of lymphoma or those who have received other anticancer therapies within three weeks prior to inclusion may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could lead to more effective treatment regimens for patients with relapsed primary CNS lymphoma.
How similar studies have performed: While the use of glucarpidase in this context is innovative, similar studies have shown promise in enhancing methotrexate treatment, suggesting potential for success.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Paris
- Hôpital Pitié-Salpêtrière — Paris, France (Recruiting)
Study contacts
- Study coordinator: Caroline HOUILLIER, MD
- Email: caroline.houillier@aphp.fr
- Phone: 01 42 16 41 60
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.