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

NCT ID: NCT06373211

Last Updated: 2025-02-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-10
• Study Completion Date: 2028-06-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early immunotherapy

Early immunotherapy with intravenous immunoglobulin, cyclophosphamide and methylprednisolone

Group Type: EXPERIMENTAL

Immunoglobulins IV (CLAYRIG)

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dimitri Psimaras, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Pitié-Salpêtrière

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Dimitri Psimaras, MD

Role: CONTACT

dimitri.psimaras@aphp.fr

+33 1 42 16 04 35

Alice LEPRINCE-LAURENGE, MD

Role: CONTACT

alice.laurenge@aphp.fr

+33 1 42 16 03 86

Facility Contacts

Dimitri Psimaras, MD

Role: primary

dimitri.psimaras@aphp.fr

Alice LEPRINCE-LAURENGE, MD

Role: backup

alice.laurenge@aphp.fr

Other Identifiers

2023-506942-22-01

Identifier Type: OTHER

Identifier Source: secondary_id

APHP230701

Identifier Type: -

Identifier Source: org_study_id