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NCT Number: NCT06373211

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

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.

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Key information

Conditions

Paraneoplastic Sensory Neuronopathy Neoplasms Paraneoplastic Syndromes

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location status: Recruiting

Location contact

Alice LEPRINCE-LAURENGE, MD

CONTACT

[email protected]

Dimitri Psimaras, MD

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Immunoglobulins IV (CLAYRIG)

Drug

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

Cyclophosphamide IV

Drug

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

Methylprednisolone IV

Drug

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 outcomes

  1. Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 months

    Time frame: At 3 months

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. Percentage of patients alive and without tumor progression at 6 months

    Time frame: At 6 months

  7. Tolerance to treatment

    Time frame: Through study completion, a maximum of 36 months

    Will be assessed by the frequency and severity of expected and unexpected adverse effects recorded during treatment

Study contacts

Contact information is provided by the study sponsor or research team.

Alice LEPRINCE-LAURENGE, MD

CONTACT

[email protected]

+33 1 42 16 03 86

Dimitri Psimaras, MD

CONTACT

[email protected]

+33 1 42 16 04 35

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: NESPA

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Apr 18, 2024
Registry last updated
Feb 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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