Early Immunotherapy with Intravenous Immunoglobulin, Cyclophosphamide and Methylprednisolone in Patients with Anti-Hu-associated Paraneoplastic Sensory Neuronopathy

Обзор

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.

Вмешательства

• Препарат 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
• Препарат 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
• Препарат 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

Первичные конечные точки

• Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 months [Срок оценки: At 3 months]

Вторичные конечные точки (7)

• Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 and 6 months [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: At 3 months and at 6 months]
• Percentage of patients with functional improvement on the modified Rankin Score (mRS) at 3 and 6 months [Срок оценки: At 3 months and at 6 months]
• Percentage of patients with functional improvement on the Barthel Index (BI) at 3 and 6 months [Срок оценки: At 3 months and at 6 months]
• Percentage of patients alive and without tumor progression at 6 months [Срок оценки: At 6 months]
• Tolerance to treatment [Срок оценки: Through study completion, a maximum of 36 months]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Hôpital Pitié-Salpêtrière — Paris

Идентификаторы

NCT: NCT06373211 · APHP230701 · 2023-506942-22-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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