CTIS2023-505933-29-00
Recruiting
Phase 1
Multicenter, open-label, phase II study in patients with immunoglobulin M monoclonal gammopathy of unknown significance and Myelin Associated Glycoprotein antibodies related polyneuropathy and Zanubrutinib Treatment - 22U-0179
ConditionsIgM monoclonal gammopathy of unknown significance (MGUS) and myelin associated glycoprotein (MAG) antibodies associated polyneuropathyMedDRA version: 21.1Level: LLTClassification code: 10066137Term: Anti-MAG neuropathy Class: 10029205Therapeutic area: Diseases [C] - Nervous System Diseases [C10]Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- IgM monoclonal gammopathy of unknown significance (MGUS) and myelin associated glycoprotein (MAG) antibodies associated polyneuropathy
- Sponsor
- niversity Medical Center Utrecht
- Enrollment
- 42
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
No summary available.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to provide written informed consent and understand and comply with the requirements of the study, No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention, Previous treatment with intravenous immunoglobulins is allowed if \> 3 months before inclusion, Previous treatment for polyneuropathy with Anti CD20 monoclonal antibody (MoAb) and/or cyclophosphamide is allowed only if given \> 6 months before inclusion. Patients without previous response to Rituximab \>6 months before inclusion can be included., Demyelinating polyneuropathy defined by the European Federation of Neurological Societies (EFNS) / Peripheral Nerve Society (PNS) guideline on management of paraproteinemic demyelinating neuropathies, Functional impairment; defined as an Inflammatory Neuropathy Cause and Treatment disability score (INCATds) of \=2, Age \= 18 years, IgM monoclonal gammopathy of unknown significance (MGUS), defined as the presence of an IgM M\-protein (detectable but \< 30 g/L) AND elevated total IgM level in serum, Presence of anti MAG antibodies \= 10\.000 titer units, measured with the Bühlmann ELISA, Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2, Adequate hematological laboratory values defined as hemoglobin \= 6\.0 mmol/L, neutrophils \> 1\.0 × 10^9/L and platelets \> 100 × 10^9/L, Adequate hepatic and renal function laboratory values defined as ASAT/ALAT \< 3 × upper limit of normal (ULN), bilirubin \< 1\.5× ULN and creatinine clearance \= 30 ml/min
Exclusion Criteria
- •Hematological malignancy e.g., known Multiple Myeloma or confirmed Waldenström’s Macroglobulinemia based on bone marrow analysis, Prior treatment with purine analogues (fludarabine or cladribine), Prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor, Major surgery within 4 weeks of study treatment, Participation in another interventional clinical trial, Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, Uncontrolled active systemic infection or recent infection requiring parenteral anti\-microbial therapy that was completed \= 14 days before the first dose of study drug, Active tuberculosis, Infection with human immunodeficiency virus (HIV), or serologic status reflecting active hepatitis B or hepatitis C infection. Patients with presence of hepatitis C virus (HCV) antibody are eligible if HCV ribonucleic acid (RNA) is undetectable. Patients with a serologic status reflecting prior or active hepatitis B cannot be included. We will test the hepatitis B surface antigen (HBsAg), anti\-hepatitis B core antibodies (anti\-HBc) and anti\-hepatitis B surface antibodies (anti\-HBs) at screening. Patients with a serological status reflecting an earlier hepatitis B vaccination (HBsAg negative / antiHBc negative / anti\-HBs positive) may be included. Other combinations are not allowed., At time of study entry, taking any medications which are strong CYP3A inhibitors (e.g., conivaptan, posaconazole, voriconazole, ketoconazole, itraconazole, clarithromycin, indinavir, lopinavir, ritonavir, telaprevir) or strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s wort), Intolerance to previous Rituximab treatment, Pregnant women, women with child\-bearing potential (WOCBP) not able or willing to prevent pregnancy and lactating women as well. WOCBP will agree to use highly effective contraception for the duration of the trial treatment and for 12 months after Rituximab treatment stop or 120 days after Zanubrutinib treatment stop, whichever has a longer duration. Participants using hormonal contraceptives (e.g., birth control pills or devices) must use a barrier method of contraception (e.g., condoms) as well., History of intolerance to the active ingredients or other ingredients of Zanubrutinib, Other known concomitant causes of chronic (demyelinating) polyneuropathy, including Charcot Marie Tooth Disease, other hereditary neuropathies, diabetes mellitus, use of amiodarone, past or current dependence on alcohol, other lymphoma or malignant blood dyscrasias, previous Guillain\-Barré syndrome, Currently active, clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease (congestive heart failure) as defined by the New York Heart Association (NYHA) Functional Classification, or history of myocardial infarction within 6 months of screening, A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening: QTcF \>450 msec (males); QTcF \>460 msec (females); History of familial long QT syndrome or known family history of Torsade de Pointes; Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study; Second degree atrioventricular (AV) block Type II, or third\-degree AV blo
Outcomes
Primary Outcomes
Not specified
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