A Phase I/II Study to Investigate the Use of VORAXAZE™ as Intended Intervention in Patients With CNSL (VALIDATE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04841434|
Recruitment Status : Recruiting
First Posted : April 12, 2021
Last Update Posted : July 19, 2022
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).
|Condition or disease||Intervention/treatment||Phase|
|CNS Lymphoma||Drug: Voraxaze Injectable Product||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Dose escalation will be performed using three dose levels of MTX.|
|Masking:||None (Open Label)|
|Official Title:||An Open Label, Phase I/II Study to Investigate the Use of VORAXAZE™ as Intended Intervention in Patients With Central Nervous System Lymphoma and With Impaired Renal Function Being Treated With High-dose Methotrexate|
|Actual Study Start Date :||June 1, 2021|
|Estimated Primary Completion Date :||August 1, 2023|
|Estimated Study Completion Date :||April 1, 2024|
Experimental: Dose escalation
Patients will receive up to 6 cycles of HD-MTX Treatment Dose escalation will be performed using three dose levels of MTX: 3.0 g/m2, 3.5 g/m2, 4.0 g/m2
Drug: Voraxaze Injectable Product
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.
Other Name: High-dose Methotrexat Infusion
- Tolerability of Voraxaze [ Time Frame: 1 year ]absence of severe non-hematological toxicity
- Efficacy of Voraxaze [ Time Frame: 1 year ]immediate and sustained reduction in plasma MTX concentration
- Dose Limiting Toxicities (DLTs) [ Time Frame: 1 year ]appearance of DLTs for each dose level of MTX
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04841434
|Contact: Susen Burock, MD||+49 (030) 450 564 firstname.lastname@example.org|
|Charité Campus Benjamin Franklin (CBF)||Recruiting|
|Berlin, Germany, 12200|
|Contact: Stefan Schwartz, MD 030 450 513382 email@example.com|