Switched Memory B-cells as a Marker for Humoral Immune System Recovery in Patients With Secondary Antibody Deficiency Due to Hematological Malignancies

Phase 4

Not yet recruiting

• Conditions: Secondary Antibody Deficiency
• Interventions: Drug: Immunoglobulin replacement therapy (IGRT)

• Registration Number: NCT05612607
• Lead Sponsor: Ottawa Hospital Research Institute

Brief Summary

Current treatment for patients with secondary antibody deficiency (SAD) is Immunoglobulin replacement therapy (IGRT). There are currently no clinical guidelines for IGRT discontinuation in patients with SAD. This study will examine the IGRT discontinuation success rate and IGRT discontinuation rate in patients.

Detailed Description

Immunoglobulin replacement therapy (IGRT) is a mainstay treatment for SAD and has been shown to reduce the risk of infection and increase quality of life in patients with SAD. Current guidelines recommend that patients with severe hypogammaglobulinemia (IgG \<4 g/L) or patients with a history of recurrent or severe infections should be offered IGRT, which can be administered intravenously on a monthly basis or more frequently by subcutaneous infusions. There are currently no clinical guidelines for IGRT discontinuation. Although research conducted at the Ottawa Hospital indicates successful discontinuation of IGRT, clinicians need a tool to predict the recovery of humoral immunity and the risk of infection in these patients in order to determine whether IGRT may be safely discontinued.

Study Timeline

• Study First Submitted: 2022-10-01
• Status Verified: 2022-11
• Study First Submitted QC: 2022-11-04
• Last Update Submitted: 2022-11-04
• Study Start: 2022-11-10
• Study First Posted: 2022-11-10
• Last Update Posted: 2022-11-10
• Primary Completion: 2023-10-10
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. History of leukemia, lymphoma, or plasma cell disease
2. Receiving IGRT for SAD for at least 12 months
3. Over 18 years of age
4. Able to provide informed consent
5. Able to speak English or French
6. Available for ongoing follow-up as required

Exclusion Criteria

1. Receiving chemotherapy or immune-oncology treatment during the study period
2. Severe infection within the last 6 months
3. Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IGRT discontinuation	Immunoglobulin replacement therapy (IGRT)	Participants will be tested to determine Switched memory B cells (SMB) levels. If SMB cells are ≥ 2%, IGRT will be discontinued. If SMB cells are \< 2%, the patient will remain on IGRT and a maximum of 40 mL of blood will be drawn again in 3-6 months to reassess SMB levels and eligibility for IGRT discontinuation.

Primary Outcome Measures

Name	Time	Method
IGRT discontinuation rate	12 months post discontinuation	IGRT discontinuation rate defined as the proportion of recruited adult patients with SAD who discontinue IGRT during the study period.
IGRT discontinuation sucess rate	12 months post discontinuation	IGRT discontinuation success rate defined as the proportion of patients with normal SMB levels who stop IGRT and experience less than or equal to 1 moderate infection and no severe infection within 12 months of IGRT discontinuation. Moderate infection will be defined as an infection that requires outpatient oral antimicrobial treatment. Severe infection will be defined as an infection that requires intravenous antimicrobial treatment and/or hospitalization.

Secondary Outcome Measures

Name	Time	Method
Cost saving potential	Through study completion, an average of 1 year	Calculated potential cost saving based on the study IGRT discontinuation rate using SMB as a marker for discontinuation.
Change in Health-Related Quality of Life	Through study completion, an average of 1 year	Change in Health-Related Quality of Life (HRQoL) before and after IGRT discontinuation. The Euroqol 5-dimension 5-level (EQ-5D-5L) questionnaire will be used to obtain HRQoL data.
Receiver operating curve (ROC)	Through study completion, an average of 1 year	We will estimate a receiver operating curve (ROC) of SMB proportion as a predictor of successful discontinuation.