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

• Status: Not yet recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: BTG International Inc.
• Treatments: Methotrexate

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.