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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04841434

Studienbeginn:
Juni 2021

Letztes Update:
01.09.2023

Wirkstoff:
Voraxaze Injectable Product

Indikation (Clinical Trials):
Lymphoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Charite University, Berlin, Germany

Collaborator:
-

Kontakt

Susen Burock, MD
Kontakt:
Phone: +49 (030) 450 564 648
E-Mail: susen.burock@charite.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Charité Campus Benjamin Franklin (CBF)
12200 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Stefan Schwartz, MD
Phone: 030 450 513382
E-Mail: stefan.schwartz@charite.de» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

MTX is used either alone or as part of a combined chemotherapy protocol either in standard or

high doses in the treatment of a range of cancers and other diseases.

Dose escalation will be performed using three dose levels of MTX:

Level 1: 3.0 g/m2 Level 2: 3.5 g/m2 Level 3: 4.0 g/m2 Up to 6 patients will be treated at

each dose level; each will receive a maximum of 6 cycles of treatment. The dose may be

increased in Cycle 3 in individual patients to the next level, if renal function is adequate

(GFR ≥ 40 mL/min, or in the case of decreased GFR, the decrease is <10% compared with the

pre-treatment value), and absence of grade 3 or 4 non-hematological toxicities.

Ein-/Ausschlusskriterien

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)

Studien-Rationale

Primary outcome:

1. Tolerability of Voraxaze (Time Frame - 1 year):
absence of severe non-hematological toxicity

2. Efficacy of Voraxaze (Time Frame - 1 year):
immediate and sustained reduction in plasma MTX concentration

Secondary outcome:

1. Dose Limiting Toxicities (DLTs) (Time Frame - 1 year):
appearance of DLTs for each dose level of MTX

2. Anti-glucarpidase antibodies (Time Frame - at screening, prior to the MTX infusion at each treatment cycle and on day 28 of the last cycle):
presence of antibodies to glucarpidase

3. MTX toxicities (Time Frame - 1 year):
incidence and severity of hematological toxicities and stomatitis after each cycle of HD-MTX treatment and renal function before each cycle of HD-MTX treatment

Geprüfte Regime

Voraxaze Injectable Product (High-dose Methotrexat Infusion):
High-dose Methotrexat Infusion: MTX is given at a dose according to the allocated dose level cohort as a 4-hour IV infusion. HD-MTX cycles (up to 6) should be repeated every 14 days, provided that the patient has recovered (i.e., hematopoietic reconstitution) between cycles. A delay of up to 28 days between cycles is permitted in order to allow patients to recover from the preceding dose of MTX. In patients with a decline of the GFR to <40 mL/min, or in the case of decreased GFR, the decrease is >50% compared with the pretreatment value, treatment will be terminated. At the start of Cycle 3 the dose of MTX can be escalated to the next level if MTX has been well-tolerated according to the criteria described under dose escalation. Voraxaze: 2000 Units in patients weighing ≤100kg and at least 20 Units per kg body weight in patients weighing >100kg is given in each HD-MTX cycle as a slow IV injection at 24 hours (+/- 2 hours) after the start of HD-MTX infusion.

Quelle: ClinicalTrials.gov

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