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

Last updated: February 13, 2025
Sponsor: Assistance Publique - Hôpitaux de Paris
Overall Status: Active - Recruiting

Phase

2

Condition

N/A

Treatment

Immunoglobulins IV (CLAYRIG)

Cyclophosphamide IV

Methylprednisolone IV

Clinical Study ID

NCT06373211
APHP230701
2023-506942-22-01
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

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 theneuromuscular junction is allowed, provided that it has a minor impact on thepatient'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

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 humanimmunoglobulins

  • Absolute contraindications to cyclophosphamide: vaccination against yellow fever inthe 3 months preceding inclusion, acute urinary infection, pre-existing hemorrhagiccystitis, urinary tract obstruction, acute bone marrow failure

  • Contraindication to methylprednisolone: live vaccines, or live attenuated vaccineswithin 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 monthspreviously

  • 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

Study Design

Total Participants: 21
Treatment Group(s): 3
Primary Treatment: Immunoglobulins IV (CLAYRIG)
Phase: 2
Study Start date:
January 10, 2025
Estimated Completion Date:
June 30, 2028

Connect with a study center

  • Hôpital Pitié-Salpêtrière

    Paris, 75013
    France

    Active - Recruiting

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