Humoral Immunodeficiency in CLL and Therapy With Subcutaneous Ig

NCT ID: NCT03730129

Last Updated: 2020-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-05

Study Completion Date

2020-07-03

Brief Summary

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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.

Detailed Description

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Conditions

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Secondary Immune Deficiency Disorder

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ig replacement

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

Group Type EXPERIMENTAL

Hizentra

Intervention Type DRUG

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

Interventions

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Hizentra

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rochester General Hospital

OTHER

Sponsor Role lead

Responsible Party

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S. Shahzad Mustafa

Associate Medical Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shahzad Mustafa, MD

Role: PRINCIPAL_INVESTIGATOR

Rochester General Hospital

Locations

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Allergy, Immunology, Rheumatology at Rochester Regional Health

Rochester, New York, United States

Site Status

Countries

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United States

References

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Chapel H, Dicato M, Gamm H, Brennan V, Ries F, Bunch C, Lee M. Immunoglobulin replacement in patients with chronic lymphocytic leukaemia: a comparison of two dose regimes. Br J Haematol. 1994 Sep;88(1):209-12. doi: 10.1111/j.1365-2141.1994.tb05002.x.

Reference Type BACKGROUND
PMID: 7803248 (View on PubMed)

Dicato M, Chapel H, Gamm H, Lee M, Ries F, Marichal S, Wirth C, Griffith H, Brennan V. Use of intravenous immunoglobulin in chronic lymphocytic leukemia. A brief review. Cancer. 1991 Sep 15;68(6 Suppl):1437-9. doi: 10.1002/1097-0142(19910915)68:6+3.0.co;2-h.

Reference Type BACKGROUND
PMID: 1878842 (View on PubMed)

Molica S, Musto P, Chiurazzi F, Specchia G, Brugiatelli M, Cicoira L, Levato D, Nobile F, Carotenuto M, Liso V, Rotoli B. Prophylaxis against infections with low-dose intravenous immunoglobulins (IVIG) in chronic lymphocytic leukemia. Results of a crossover study. Haematologica. 1996 Mar-Apr;81(2):121-6.

Reference Type BACKGROUND
PMID: 8641639 (View on PubMed)

Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O. Immunoglobulin prophylaxis in hematological malignancies and hematopoietic stem cell transplantation. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD006501. doi: 10.1002/14651858.CD006501.pub2.

Reference Type BACKGROUND
PMID: 18843719 (View on PubMed)

Dhalla F, Lucas M, Schuh A, Bhole M, Jain R, Patel SY, Misbah S, Chapel H. Antibody deficiency secondary to chronic lymphocytic leukemia: Should patients be treated with prophylactic replacement immunoglobulin? J Clin Immunol. 2014 Apr;34(3):277-82. doi: 10.1007/s10875-014-9995-5. Epub 2014 Feb 21.

Reference Type BACKGROUND
PMID: 24557494 (View on PubMed)

Ueda M, Berger M, Gale RP, Lazarus HM. Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation. Blood Rev. 2018 Mar;32(2):106-115. doi: 10.1016/j.blre.2017.09.003. Epub 2017 Sep 19.

Reference Type BACKGROUND
PMID: 28958644 (View on PubMed)

Sanchez-Ramon S, Dhalla F, Chapel H. Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy. Front Immunol. 2016 Aug 22;7:317. doi: 10.3389/fimmu.2016.00317. eCollection 2016.

Reference Type BACKGROUND
PMID: 27597852 (View on PubMed)

Twomey JJ. Infections complicating multiple myeloma and chronic lymphocytic leukemia. Arch Intern Med. 1973 Oct;132(4):562-5. No abstract available.

Reference Type BACKGROUND
PMID: 4542660 (View on PubMed)

Oscier D, Dearden C, Eren E, Fegan C, Follows G, Hillmen P, Illidge T, Matutes E, Milligan DW, Pettitt A, Schuh A, Wimperis J; British Committee for Standards in Haematology. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia. Br J Haematol. 2012 Dec;159(5):541-64. doi: 10.1111/bjh.12067. Epub 2012 Oct 11. No abstract available.

Reference Type BACKGROUND
PMID: 23057493 (View on PubMed)

Lachance S, Christofides AL, Lee JK, Sehn LH, Ritchie BC, Shustik C, Stewart DA, Toze CL, Haddad E, Vinh DC. A Canadian perspective on the use of immunoglobulin therapy to reduce infectious complications in chronic lymphocytic leukemia. Curr Oncol. 2016 Feb;23(1):42-51. doi: 10.3747/co.23.2810. Epub 2016 Feb 18.

Reference Type BACKGROUND
PMID: 26966403 (View on PubMed)

Friman V, Winqvist O, Blimark C, Langerbeins P, Chapel H, Dhalla F. Secondary immunodeficiency in lymphoproliferative malignancies. Hematol Oncol. 2016 Sep;34(3):121-32. doi: 10.1002/hon.2323. Epub 2016 Jul 12.

Reference Type BACKGROUND
PMID: 27402426 (View on PubMed)

Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia; Gale RP, Chapel HM, Bunch C, Rai KR, Foon K, Courter SG, Tait D. Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial. N Engl J Med. 1988 Oct 6;319(14):902-7. doi: 10.1056/NEJM198810063191403.

Reference Type BACKGROUND
PMID: 2901668 (View on PubMed)

Looney RJ, Huggins J. Use of intravenous immunoglobulin G (IVIG). Best Pract Res Clin Haematol. 2006;19(1):3-25. doi: 10.1016/j.beha.2005.01.032.

Reference Type BACKGROUND
PMID: 16377538 (View on PubMed)

Berger M. Adverse effects of IgG therapy. J Allergy Clin Immunol Pract. 2013 Nov-Dec;1(6):558-66. doi: 10.1016/j.jaip.2013.09.012. Epub 2013 Oct 31.

Reference Type BACKGROUND
PMID: 24565701 (View on PubMed)

Gardulf A. Immunoglobulin treatment for primary antibody deficiencies: advantages of the subcutaneous route. BioDrugs. 2007;21(2):105-16. doi: 10.2165/00063030-200721020-00005.

Reference Type BACKGROUND
PMID: 17402794 (View on PubMed)

Lingman-Framme J, Fasth A. Subcutaneous immunoglobulin for primary and secondary immunodeficiencies: an evidence-based review. Drugs. 2013 Aug;73(12):1307-19. doi: 10.1007/s40265-013-0094-3.

Reference Type BACKGROUND
PMID: 23861187 (View on PubMed)

Compagno N, Cinetto F, Semenzato G, Agostini C. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients. Haematologica. 2014 Jun;99(6):1101-6. doi: 10.3324/haematol.2013.101261. Epub 2014 Mar 28.

Reference Type BACKGROUND
PMID: 24682509 (View on PubMed)

Vacca A, Melaccio A, Sportelli A, Solimando AG, Dammacco F, Ria R. Subcutaneous immunoglobulins in patients with multiple myeloma and secondary hypogammaglobulinemia: a randomized trial. Clin Immunol. 2018 Jun;191:110-115. doi: 10.1016/j.clim.2017.11.014. Epub 2017 Nov 28.

Reference Type BACKGROUND
PMID: 29191714 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34653210 (View on PubMed)

Other Identifiers

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CIC1850-A-18

Identifier Type: -

Identifier Source: org_study_id

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