CNS LymphomaPhase 1/2VALIDATENCT04841434
A Phase I/II Study to Investigate the Use of VORAXAZE™ As Intended Intervention in Patients with CNSL
A Phase 1/2 study testing Voraxaze Injectable Product in people with CNS Lymphoma, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CNS Lymphoma
- What is being tested?
- Voraxaze Injectable Product
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jun 2021to 1 Dec 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Conditions
- CNS Lymphoma
- Being tested
- Voraxaze Injectable Product
- Keywords
- impaired renal function
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Voraxaze Injectable ProductDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | 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 Receives: Drug: Voraxaze Injectable Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability of Voraxaze
absence of severe non-hematological toxicity
Measured: 1 year
Efficacy of Voraxaze
immediate and sustained reduction in plasma MTX concentration
Measured: 1 year
Secondary outcomes (3)
Dose Limiting Toxicities (DLTs)
appearance of DLTs for each dose level of MTX
Measured: 1 year
Anti-glucarpidase antibodies
presence of antibodies to glucarpidase
Measured: at screening, prior to the MTX infusion at each treatment cycle and on day 28 of the last cycle
MTX toxicities
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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2021
- Study start1 Jun 2021
- Primary completion1 Dec 2024
- Study completion1 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CNS LymphomaStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Dose escalation will be performed using three dose levels of MTX.
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefan Schwartz, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04841434
- Sponsor's protocol ID
- CNS-Lymphoma-Vorax-1
- Acronym
- VALIDATE
- Status last verified
- Jan 2025
- First submitted
- 8 Apr 2021
- Last updated
- 6 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04841434
- Acronym / sponsor ID
- VALIDATE / CNS-Lymphoma-Vorax-1
- Conditions
- CNS Lymphoma
- Keywords
- impaired renal function
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 1 Dec 2024 (actual)
- Study completion
- 1 Dec 2024 (actual)
- First posted
- 12 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Dose escalation will be performed using three dose levels of MTX.
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: Voraxaze Injectable ProductPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (11 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Voraxaze Injectable ProductAlso: High-dose Methotrexat InfusionHigh-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. | Drug | Dose escalation |
Primary outcome
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
3 secondary outcomes
Dose Limiting Toxicities (DLTs)
Time frame: 1 year
Anti-glucarpidase antibodies
Time frame: at screening, prior to the MTX infusion at each treatment cycle and on day 28 of the last cycle
MTX toxicities
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Voraxaze Injectable Product in people with CNS Lymphoma, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerability of Voraxaze (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2025.