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
|
Sponsor:
Charite University, Berlin, Germany
Information provided by (Responsible Party):
Stefan Schwartz, Charite University, Berlin, Germany
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief 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).
| 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 |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | Dose escalation will be performed using three dose levels of MTX. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Lymphoma
| Arm | Intervention/treatment |
|---|---|
|
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 |
Primary Outcome Measures :
- 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
Secondary Outcome Measures :
- 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
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
Information from the National Library of Medicine
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
Contacts
| Contact: Susen Burock, MD | +49 (030) 450 564 648 | susen.burock@charite.de |
Locations
| Germany | |
| Charité Campus Benjamin Franklin (CBF) | Recruiting |
| Berlin, Germany, 12200 | |
| Contact: Stefan Schwartz, MD 030 450 513382 stefan.schwartz@charite.de | |
Sponsors and Collaborators
Charite University, Berlin, Germany
| Responsible Party: | Stefan Schwartz, PD Dr. med., Charite University, Berlin, Germany |
| ClinicalTrials.gov Identifier: | NCT04841434 |
| Other Study ID Numbers: |
CNS-Lymphoma-Vorax-1 |
| First Posted: | April 12, 2021 Key Record Dates |
| Last Update Posted: | July 19, 2022 |
| Last Verified: | July 2022 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Stefan Schwartz, Charite University, Berlin, Germany:
|
impaired renal function |
Additional relevant MeSH terms:
|
Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Methotrexate Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs |
Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors |