Dose Dense Re-challenge of High Dose Methotrexate With Glucarpidase for Relapsed Primary Central Nervous System Lymphoma

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Nov 15, 2021

Keywords

ClinConnect Summary

This clinical trial is investigating a new approach to treat patients with relapsed primary central nervous system lymphoma (PCNSL), a type of cancer that affects the brain and spinal cord. The study is testing whether a drug called glucarpidase can be used after high doses of methotrexate (a common chemotherapy drug) to help reduce the time between treatments. This could allow patients to receive more intense treatment with fewer side effects and shorten their hospital stays.

To participate in the trial, patients need to be at least 18 years old and have had a previous complete response to methotrexate treatment lasting at least six months. They should not have any other significant health issues, such as active viral infections or other cancers. Participants will receive the treatments in a controlled setting, and their health will be monitored closely throughout the study. If you or a loved one are considering joining this trial, it's important to discuss it with your healthcare provider to see if it’s the right option for you.

Gender

ALL

Eligibility 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.