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

NCT06373211 | Recruiting Phase 2

• 2 other identifiers: APHP2307012023-506942-22-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Paraneoplastic Sensory Neuronopathy

Keywords

Sensory neuronopathy; Paraneoplastic syndrome; Early immunotherapy

Outcome Measures

Primary Outcomes (1)

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

  At 3 months

Secondary Outcomes (7)

• Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 and 6 months

  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

  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

  At 3 months and at 6 months

• Percentage of patients with functional improvement on the modified Rankin Score (mRS) at 3 and 6 months

  At 3 months and at 6 months

• Percentage of patients with functional improvement on the Barthel Index (BI) at 3 and 6 months

  At 3 months and at 6 months

Study Arms (1)

Early immunotherapy

EXPERIMENTAL

Early immunotherapy with intravenous immunoglobulin, cyclophosphamide and methylprednisolone

Drug: Immunoglobulins IV (CLAYRIG); Drug: Cyclophosphamide IV; Drug: Methylprednisolone IV

Interventions

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

Early immunotherapy

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

Early immunotherapy

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

Early immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

MeSH Terms

Conditions

Paraneoplastic Syndromes

Interventions

gamma-Globulins

Condition Hierarchy (Ancestors)

Neoplasms

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dimitri Psimaras, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dimitri Psimaras, MD

CONTACT

+33 1 42 16 04 35; dimitri.psimaras@aphp.fr

Alice LEPRINCE-LAURENGE, MD

CONTACT

+33 1 42 16 03 86; alice.laurenge@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 18, 2024
• Study Start: January 10, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (1)