Ignite Creation Date:
2025-12-25 @ 2:18 AM
Ignite Modification Date:
2025-12-31 @ 8:07 PM
Study NCT ID:
NCT04841434
Status:
COMPLETED
Last Update Posted:
2025-01-06
First Post:
2021-04-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Phase I/II Study to Investigate the Use of VORAXAZE™ As Intended Intervention in Patients with CNSL
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D051437', 'term': 'Renal Insufficiency'}], 'ancestors': [{'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Dose escalation will be performed using three dose levels of MTX.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-06-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2024-12-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-01-03', 'studyFirstSubmitDate': '2021-04-08', 'studyFirstSubmitQcDate': '2021-04-08', 'lastUpdatePostDateStruct': {'date': '2025-01-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-04-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-12-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Tolerability of Voraxaze', 'timeFrame': '1 year', 'description': 'absence of severe non-hematological toxicity'}, {'measure': 'Efficacy of Voraxaze', 'timeFrame': '1 year', 'description': 'immediate and sustained reduction in plasma MTX concentration'}], 'secondaryOutcomes': [{'measure': 'Dose Limiting Toxicities (DLTs)', 'timeFrame': '1 year', 'description': 'appearance of DLTs for each dose level of MTX'}, {'measure': 'Anti-glucarpidase antibodies', 'timeFrame': 'at screening, prior to the MTX infusion at each treatment cycle and on day 28 of the last cycle', 'description': 'presence of antibodies to glucarpidase'}, {'measure': 'MTX toxicities', 'timeFrame': '1 year', 'description': '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'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['impaired renal function'], 'conditions': ['CNS Lymphoma']}, 'descriptionModule': {'briefSummary': '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.\n\nPatients 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).', 'detailedDescription': '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.\n\nDose escalation will be performed using three dose levels of MTX:\n\nLevel 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Primary or secondary CNSL (PCNSL or SCNSL) confirmed by histology or cytology.\n* 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.\n* Age ≥ 18 years (male or female).\n* Life expectancy \\>3 months.\n* Adequate organ function (i.e., bone marrow, liver, lungs) allowing intensive chemotherapy with MTX.\n* Adequate clinical pathology values:\n* Absolute neutrophil count ≥1.0 x 109/L, hemoglobin ≥9mg/dL (transfusion allowed), platelets ≥100 x 109/L.\n* Total bilirubin ≤1.5x the upper limit of normal except for patients with known Gilbert syndrome.\n* Alanine amino-transferase (ALT) and aspartate amino-transferase (AST) ≤2x the upper limit of normal.\n* Alkaline phosphatase ≤2x the upper limit of normal.\n* Prothrombin time within the normal range for the institution.\n* Signed informed consent by the patient or legal representative prior to start of any study specific procedure.\n* 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.\n\nExclusion Criteria:\n\n* 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.\n* Prior brain radiotherapy within 28 days of first dose of the study drug.\n* Concurrent illness interfering with hydration (i.e., relevant congestive heart failure, SIADH syndrome).\n* Relevant third space (i.e., pleural effusion, ascites, extended edema) precluding HD-MTX treatment.\n* Obesity (body mass index \\>30 kg/m2).\n* Uncontrolled diabetes.\n* Active hepatitis.\n* HIV-infection.\n* Pregnant or lactating woman.\n* Participation in any other clinical trial either 1 month prior to or during this study.\n* Previous intolerance to any of the drugs used in this study (i.e., MTX, LV)'}, 'identificationModule': {'nctId': 'NCT04841434', 'acronym': 'VALIDATE', 'briefTitle': 'A Phase I/II Study to Investigate the Use of VORAXAZE™ As Intended Intervention in Patients with CNSL', 'organization': {'class': 'OTHER', 'fullName': 'Charite University, Berlin, Germany'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'CNS-Lymphoma-Vorax-1'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dose escalation', 'description': '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', 'interventionNames': ['Drug: Voraxaze Injectable Product']}], 'interventions': [{'name': 'Voraxaze Injectable Product', 'type': 'DRUG', 'otherNames': ['High-dose Methotrexat Infusion'], 'description': '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.', 'armGroupLabels': ['Dose escalation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '12200', 'city': 'Berlin', 'country': 'Germany', 'facility': 'Charité Campus Benjamin Franklin (CBF)', 'geoPoint': {'lat': 52.52437, 'lon': 13.41053}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Charite University, Berlin, Germany', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'PD Dr. med.', 'investigatorFullName': 'Stefan Schwartz', 'investigatorAffiliation': 'Charite University, Berlin, Germany'}}}}