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

Phase 2

Not yet recruiting

• Conditions: Paraneoplastic Sensory Neuronopathy
• Interventions: Drug: Immunoglobulins IV (CLAYRIG); Drug: Cyclophosphamide IV; Drug: Methylprednisolone IV

• Registration Number: NCT06373211
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-04
• Study First Submitted: 2024-04-15
• Study First Submitted QC: 2024-04-17
• Last Update Submitted: 2024-04-17
• Study First Posted: 2024-04-18
• Last Update Posted: 2024-04-18
• Study Start: 2024-06
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 21

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Early immunotherapy	Cyclophosphamide IV	Early immunotherapy with intravenous immunoglobulin, cyclophosphamide and methylprednisolone
Early immunotherapy	Immunoglobulins IV (CLAYRIG)	Early immunotherapy with intravenous immunoglobulin, cyclophosphamide and methylprednisolone
Early immunotherapy	Methylprednisolone IV	Early immunotherapy with intravenous immunoglobulin, cyclophosphamide and methylprednisolone

Primary Outcome Measures

Name	Time	Method
Percentage of patients with clinical improvement on the ONLS (Overall Neuropathy Limitations Scale) at 3 months	At 3 months

Secondary Outcome Measures

Name	Time	Method
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
Percentage of patients alive and without tumor progression at 6 months	At 6 months
Tolerance to treatment	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

Trial Locations

Locations (1)

Hôpital Pitié-Salpêtrière; 🇫🇷 Paris, France