CNS lymphoma (CNSL) being treated with HD-MTX in patients with impaired renal function
Conditions
Interventions
Trade Name: Voraxaze
Product Name: Voraxaze
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GLUCARPIDASE
CAS Number: 9074-87-7
Concentration unit: U unit(s)
Concentration ty
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion 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: o - Absolute neutrophil count =1.0 x 109/L, hemoglobin =9mg/dL (transfusion allowed), platelets =100 x 109/L. o - Total bilirubin =1.5x the upper limit of normal except for patients with known Gilbert syndrome. o - Alanine amino-transferase (ALT) and aspartate amino-transferase (AST) =2x the upper limit of normal. o - Alkaline phosphatase =2x the upper limit of normal. o - 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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 9 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
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) • The person concerned has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities • Persons who may be dependent on the sponsor or investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To demonstrate tolerability of intended intervention with VoraxazeTM, in addition to LV, in patients with renal impairment or renal failure during previous HD-MTX therapy. •To measure the efficacy of VoraxazeTM in lowering the MTX blood levels in patients who are being treated with HD-MTX and LV. •To demonstrate the feasibility and safety of escalating doses of HD-MTX in patients with renal impairment or renal failure by use of intended intervention with VoraxazeTM, in addition to LV. •To assess the immunological response to Voraxaze after repeated use and the effect of any response on the safety and efficacy of VoraxazeTM. •To describe levels of MTX and DAMPA in plasma (and CSF in selected patients) following Voraxaze administration. •To assess tolerability of HD-MTX in patients with renal impairment or renal failure in the setting of Voraxaze administration. ;Secondary Objective: - To demonstrate the feasibility and potential benefit of escalating doses of HD-MTX in patients by use of intended intervention with Voraxaze, in addition to LV - To assess the immunological response to Voraxaze after repeated use and the effect of any response on the safety and efficacy of Voraxaze - To demonstrate that HD-MTX with VoraxazeTM allows schedule adherence with 6 cycles HD-MTX;Primary end point(s): •To demonstrate tolerability (i.e. absence of severe non-hematological toxicity) of intended intervention with repeated doses of VoraxazeTM, in addition to leucovorin (LV), in patients with renals impairment or renal failure during previous HD-MTX therapy. •To measure the efficacy of VoraxazeTM in patients with renal impairment or renal failure who are being treated with HD-MTX and LV as determined by plasma MTX level reduction. ;Timepoint(s) of evaluation of this end point: During visits at defined timepoints as per protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To demonstrate the feasibility and potential benefit of escalating doses of HD-MTX in patients by use of intended intervention with VoraxazeTM, in addition to LV. • To assess the immunological response to VoraxazeTM after repeated use and the effect of any response on the safety and efficacy of VoraxazeTM. • To demonstrate that HD-MTX with VoraxazeTM allows schedule adherence with 6 cycles HD-MTX ;Timepoint(s) of evaluation of this end point: During visits at defined timepoints as per protocol | — |
Countries
Germany
Contacts
Public ContactUlrich Keilholz
Charité Universitätsmedizin Berlin
Outcome results
None listed