Early Immunotherapy with Intravenous Immunoglobulin, Cyclophosphamide and Methylprednisolone in Patients with Anti-Hu-associated Paraneoplastic Sensory Neuronopathy
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Immunoglobulins IV (CLAYRIG), Cyclophosphamide IV, Methylprednisolone IV.
- Who it may be relevant to
- Registry conditions: Paraneoplastic Sensory Neuronopathy. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
Paraneoplastic Neurological Syndromes are rare autoimmune complications linked to the presence of systemic cancer. Despite their autoimmune origin, they have historically shown little response to immunotherapy. The reason for this failure is probably related to too late administration of immunotherapy, at a stage where the inflammation has already disappeared and irreversible neuronal loss has occurred. The protocol focuses on patients with anti-Hu antibody sensory neuronopathy. This single arm trial consists of an early immunotherapy combining Intravenous Immunoglobulin (IVIG) for 3 months, cyclophosphamide and methylprednisolone for 6 months, at the rate of 1 cycle per month. The percentage of patients with clinical improvement will be evaluated (ONLS) at 3 months. The tolerance of the treatment will also be evaluated as well as other functional scales at 3 and 6 months.
Interventions
- Drug Immunoglobulins IV (CLAYRIG)
Patients will be treated with cycles of : \- Intravenous (IV) immunoglobulins: 2 g/kg per cycle, over 3 to 5 days (D1 to D3 or D5). Cycles will be administered every 4 weeks for a total of 3 first cycles - Drug Cyclophosphamide IV
Patients will be treated with cycles of : \- Cyclophosphamide IV: 1 g on the first day (D1). Cycles will be administered every 4 weeks for a total of 6 cycles - Drug Methylprednisolone IV
Patients will be treated with cycles of : Methylprednisolone IV: 1 g/day for 3 days (D1 to D3). Cycles will be administered every 4 weeks for a total of 6 cycles
Primary outcome measures
- Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 months [Time frame: At 3 months]
Secondary outcome measures (7)
- Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 and 6 months [Time frame: At 3 months and at 6 months]
- Percentage of patients with improvement in the ataxic component on the Score of Ataxia scale at 3 and 6 months [Time frame: At 3 months and at 6 months]
- Percentage of patients with improvement in neuropathic pain on the Numeric Rating Scale (NRS) at 3 and 6 months [Time frame: At 3 months and at 6 months]
- Percentage of patients with functional improvement on the modified Rankin Score (mRS) at 3 and 6 months [Time frame: At 3 months and at 6 months]
- Percentage of patients with functional improvement on the Barthel Index (BI) at 3 and 6 months [Time frame: At 3 months and at 6 months]
- Percentage of patients alive and without tumor progression at 6 months [Time frame: At 6 months]
- Tolerance to treatment [Time frame: Through study completion, a maximum of 36 months]
Eligibility criteria
Inclusion criteria
- Age ≥ 18 years old
- "Possible" sensory neuronopathy according to the criteria of Camdessanché et al. \[2\] with ONLS score ≥ 1
- Dominant picture of sensory ataxia (damage to the central nervous system and/or the neuromuscular junction is allowed, provided that it has a minor impact on the patient's disability)
- Positive anti-Hu antibodies in blood and/or cerebrospinal fluid
- Outpatient (modified Rankin Score (mRS) 2 or 3)
- Onset of neurological symptoms less than 3 months ago
- Free, informed, written and signed consent
- Affiliation to a social security or beneficiary scheme (except AME)
Exclusion criteria
- Known hypersensitivity to one of the treatments under study, to their metabolites, or to one of the excipients
- Absolute contraindications to IVIg: selective IgA deficiency, known thrombophilia, patients suffering from type I or II hyperprolinemia, hypersensitivity to human immunoglobulins
- Absolute contraindications to cyclophosphamide: vaccination against yellow fever in the 3 months preceding inclusion, acute urinary infection, pre-existing hemorrhagic cystitis, urinary tract obstruction, acute bone marrow failure
- Contraindication to methylprednisolone: live vaccines, or live attenuated vaccines within 3 months, infectious state or evolving virus (hepatitis, herpes, chickenpox, shingles)
- More than two courses of IVIg administered within 3 months before recruitment
- Other concomitant immunotherapy
- Other cause of immunosuppression (acquired or congenital)
- Treatment with checkpoint inhibitors in progress or completed less than 3 months previously
- Woman or man without effective contraception
- Pregnant or breastfeeding woman
- History of psychiatric or general illnesses that may contraindicate treatment
- Patients unable to complete the follow-up required by the study
- Patients under guardianship or curatorship
- Patient deprived of liberty by a judicial or administrative decision
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
France · 1 center
- Hôpital Pitié-Salpêtrière — Paris
Identifiers
NCT: NCT06373211 · APHP230701 · 2023-506942-22-01