Humoral Immunodeficiency in CLL and Therapy With Subcutaneous Ig

NCT03730129 | Completed Phase 2 FDA Drug

• 1 other identifier: CIC1850-A-18
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with chronic lymphocytic leukemia (CLL) are at increased risk of infections as compared to age matched controls, with infections being a major cause of morbidity and mortality. Previous studies have shown that patients with CLL have both hypogammaglobinemia and impaired humoral immunity as defined by vaccine responses to both polysaccharide and peptide antigens. Attempts at decreasing infections in CLL have included therapy with prophylactic antibiotics and intravenous immunoglobulin. In general clinical practice and in previous studies, patients have started IV immunoglobulin replacement therapy if they have a history of serious infection or hypogammaglobinemia (defined as Immunoglobulin G below 500-600 g/dL), but vaccine responses have not been evaluated. This study will identify CLL patients with humoral immunodeficiency by checking both Ig levels and vaccines responses. In patients with impaired humoral immunity, the investigators will use subcutaneous immunoglobulin replacement to show this intervention will increase Ig levels, protective antibody titers, and be well tolerated.

Conditions

Secondary Immune Deficiency Disorder

Keywords

chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (2)

• Identify patients with CLL with humoral immunodeficiency despite serum IgG > 500 mg/dL.

  Incidence of humoral immunodeficiency

  10 months

• Number of patients who increase IgG to above 700 mg/dL

  Effectiveness of Hizentra to change IgG levels

  10 months

Secondary Outcomes (4)

• Number of patients who increase diphtheria IgG to above 0.1 IU/mL, tetanus IgG to above 0.1 IU/mL, and IgG to streptococcus pneumonia to above 1.3 mcg/mL

  10 months

• Number of subjects with treatment-related adverse effects as assessed by CTCAE v4.0

  10 months

• Quality of life (Short Form 36) on subcutaneous Ig replacement therapy a 0-100 scale, with lower scores indicating higher disability/lower quality of life

  10 months

• Track the number of infections requiring antibiotics, further characterized per severity as defined in previous studies

  10 months

Study Arms (1)

Ig replacement

EXPERIMENTAL

Subjects will receive Hizentra 0.4 mg/kg subq once weekly.

Drug: Hizentra

Interventions

Hizentra DRUG

Subjects will receive Hizentra 0.4 mg/kg qweekly subcutaneously for 6 months (24 weeks)

Ig replacement

Eligibility Criteria

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

You may qualify if:

• Diagnosis of chronic lymphocytic leukemia
• Medically stable, with expected survival of \> 1 year
• Able to understand and willingness to sign a written informed consent
• Able to comply with study procedures

You may not qualify if:

• Previously diagnosed primary immunodeficiency
• Additional immunosuppressive states as assessed by the primary or co investigators
• Ongoing therapy with Ig replacement
• Serum IgG \< 500 mg/dL

Sponsors & Collaborators

• Rochester General Hospital: lead

Study Sites (1)

Allergy, Immunology, Rheumatology at Rochester Regional Health

Rochester, New York, 14607, United States

Location

Related Publications (19)

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  PMID: 4542660 BACKGROUND

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  PMID: 1878842 BACKGROUND

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  PMID: 8641639 BACKGROUND

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  PMID: 18843719 BACKGROUND

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  PMID: 28958644 BACKGROUND

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  PMID: 27597852 BACKGROUND

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  PMID: 27402426 BACKGROUND

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• Mustafa SS, Jamshed S, Vadamalai K, Ramsey A. Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia. PLoS One. 2021 Oct 15;16(10):e0258529. doi: 10.1371/journal.pone.0258529. eCollection 2021.

  PMID: 34653210 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Hizentra

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shahzad Mustafa, MD

  Rochester General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Medical Director

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: November 5, 2018
• Study Start: November 5, 2018
• Primary Completion: July 3, 2020
• Study Completion: July 3, 2020
• Last Updated: August 26, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)