Rituximab and Abatacept Effectiveness in Differential Treatment of Interstitial Lymphocytic Lung Disease in Children With Primary Immunodeficiencies.

Retrospective Chart Review of Children With Primary Immunodeficiencies (PID) Who Received Targeted Therapy of Interstitial Lymphocytic Lung Disease (ILLD) With Abatacept or Rituximab.

The rationale for this retrospective study is to evaluate the efficacy and safety of abatacept and rituximab treatment of ILLD in a cohort of pediatric patients with different forms of PID, who received one of the two therapy regimens predominantly based on the lesions histopathology.

Study Overview

• Status: Unknown
• Conditions: Interstitial Lymphocytic Lung Disease
• Intervention / Treatment: Drug: Rituximab; Drug: Abatacept

Detailed Description

Primary immunodeficiencies (PID) represent a heterogeneous group of more than 400 inherited conditions with associated immune dysfunctions. Though severe recurrent/chronic infections are the main cause of mortality and morbidity in PID, immune dysregulation manifesting with oncological and autoimmune or autoinflammatory conditions involving various organs and systems have been the focus of research in the recent years.

The interstitial lymphocytic lung disease (ILLD) is one of the recently characterized non-malignant PID complications. Immune dysregulation in ILLD causes reactive bronchi-associated lymphoid tissue (BALT) hyperplasia that manifests in several pathomorphological forms: follicular bronchiolitis (FB), nodular lymphoid hyperplasia (NLH), and lymphocytic interstitial pneumonia (LIP). Treatment of ILLD patients with various immunosuppressive drugs leads to inconsistent results ranging from partial\transient effect to no effect at all and has been often associated with adverse effects and an increase in infections' rate. Therefore there is a need for targeted therapy of ILLD. In small cohorts of adult PID patients rituximab in combination with azathioprine proved to be effective. Yet, the reports are scarce and there is currently no consensus on ILLD treatment, especially in children.

The study will collect and analyze information on the effectiveness and safety of ILLD monotherapy with rituximab or abatacept, chosen predominantly based on the pathomorphological characteristics of lymphoid infiltration, as well as genetic defects, in a cohort of pediatric patients with PID.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 117198
    • Recruiting
    • Dmitry Rogachev National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology
    • Contact: Anna Shcherbina, MD, PhD; Phone Number: 6299 +7(495)2876570; Email: shcher26@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients with interstitial lymphocytic lung disease treated in Dmitry Rogachev National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

Description

Inclusion Criteria:

1. Histological and/or radiological diagnosis of ILLD.
2. Treatment with rituximab or abatacept for at least 12 months.
3. No signs of ongoing infectious pulmonary process at the start of the treatment.
4. Regular IG substitution with trough IgG levels > 5g/l.

Exclusion criteria are nonadherence to therapy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
group 1(rituximab)	Drug: Rituximab; 375 mg/m2 as 4 weekly consecutive i.v. infusions with subsequent infusions of 375 mg/m2 performed every 3 months for 12 months.
group 2 (abatacept)	Drug: Abatacept; 10 mg/kg i.v. every 2 weeks twice, then every 4 weeks for 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dynamics of severity clinical and radiological symptoms	Dynamics of severity clinical and radiological symptoms of ILLD using scale score.	before the time the first dose of study treatment was administered
Dynamics of severity clinical and radiological symptoms	Dynamics of severity clinical and radiological symptoms of ILLD using scale score.	3 months of treatment
Dynamics of severity clinical and radiological symptoms	Dynamics of severity clinical and radiological symptoms of ILLD using scale score.	6 months of treatment
Dynamics of severity clinical and radiological symptoms	Dynamics of severity clinical and radiological symptoms of ILLD using scale score.	1 year of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events		from the time the first dose of study treatment was administered until 12 mo of treatment
quality of life of patients	The quality of life of patients before and after therapy	before the time the first dose of study treatment was administered until 12 mo of treatment

Collaborators and Investigators

• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): October 1, 2020
• Last Update Submitted That Met QC Criteria: September 25, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: treatment; children; rituximab; abatacept; primary immunodeficiency; interstitial lymphocytic lung disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Genetic Diseases, Inborn; Lung Diseases; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Rituximab; Abatacept
• Other Study ID Numbers: NCPHOI-2020-08

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No