A Phase I/II Study to Investigate the Use of VORAXAZE™ as Intended Intervention in Patients With CNSL

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I-II trial is intented to demonstrate tolerability (i.e. absence of severe non-hematological toxicity) and efficacy of intended intervention with repeated doses of Voraxaze, in addition to leucovorin (LV), in patients with renal impairment or renal failure during previous HD-MTX therapy.

Patients will receive up to 6 cycles of HD-MTX treatment with 14 days between cycles (a maximum delay of 28 days is permitted in order to allow time for a patient to recover from the previous cycle).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Charite University, Berlin, Germany
• Treatments: Methotrexate

Criteria

Inclusion Criteria:

• Primary or secondary CNSL (PCNSL or SCNSL) confirmed by histology or cytology.

• Renal insufficiency defined as a glomerular filtration rate (GFR, assessed by CKD-EPI or MDRD equation) of 40-80 mL/min or patients with a GFR >80mL/min who have experienced renal failure, defined as doubling of the serum creatinine compared to the baseline value during a previous HD-MTX treatment.

• Age ≥ 18 years (male or female).

• Life expectancy >3 months.

• Adequate organ function (i.e., bone marrow, liver, lungs) allowing intensive chemotherapy with MTX.

• Adequate clinical pathology values:

• Absolute neutrophil count ≥1.0 x 109/L, hemoglobin ≥9mg/dL (transfusion allowed), platelets ≥100 x 109/L.

• Total bilirubin ≤1.5x the upper limit of normal except for patients with known Gilbert syndrome.

• Alanine amino-transferase (ALT) and aspartate amino-transferase (AST) ≤2x the upper limit of normal.

• Alkaline phosphatase ≤2x the upper limit of normal.

• Prothrombin time within the normal range for the institution.

• Signed informed consent by the patient or legal representative prior to start of any study specific procedure.

• Females of childbearing potential and males must be willing and able to use an adequate method of contraception to avoid pregnancy for the duration of the study in such a manner that the risk of pregnancy is minimized. Acceptable contraceptives include intra-uterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.

Exclusion Criteria:

• Ongoing or expected need for therapy with drugs interfering with MTX-clearance (i.e., beta-lactam antibiotics, NSAIDs, probenicid, salicylates, sulphonamides) or other nephrotoxic drugs.

• Prior brain radiotherapy within 28 days of first dose of the study drug.

• Concurrent illness interfering with hydration (i.e., relevant congestive heart failure, SIADH syndrome).

• Relevant third space (i.e., pleural effusion, ascites, extended edema) precluding HD-MTX treatment.

• Obesity (body mass index >30 kg/m2).

• Uncontrolled diabetes.

• Active hepatitis.

• HIV-infection.

• Pregnant or lactating woman.

• Participation in any other clinical trial either 1 month prior to or during this study.

• Previous intolerance to any of the drugs used in this study (i.e., MTX, LV)