Humoral Immunodeficiency With Rituximab and Therapy With Subcutaneous Ig

Secondary Immune Deficiency Clinical Trial

Official title:

The Use of 20% Subcutaneous Immunoglobulin Replacement Therapy in Patients With B Cell Non Hodgkin's Lymphoma With Humoral Immune Dysfunction After Treatment With Rituximab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03211065
• Other study ID #: BT16-34083
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 21, 2017
• Est. completion date: November 1, 2019

Study information

• Verified date: August 2020
• Source: Rochester General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To study the use of subcutaneous (injected under the skin) immunoglobulin replacement therapy (replacement of antibodies, which are infection-fighting proteins) in patients with a type of blood cancer called lymphoma, who have been treated with rituximab (a type of chemotherapy) and have an abnormal immune system putting them at increased risk of infection.

Description:

The investigators propose evaluating patients with B cell non-Hodgkin's lymphoma treated with rituximab within the past 2 years with baseline immunoglobulin levels and vaccine responses to polysaccharide (pneumococcus, meningococcus) and peptide (tetanus, diphtheria) antigens. Patients with impaired vaccine responses may benefit most from immunoglobulin prophylaxis and will be proactively started on 20% subcutaneous replacement therapy. This study is novel in that it will stratify patients according to their humoral response to polysaccharide and peptide vaccines, and will proactively initiate therapy with the new 20% subcutaneous immunoglobulin in those with impaired humoral response rather than starting it after infections occur. This will potentially lead to decreased infections and improved quality of life.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 1, 2019
• Est. primary completion date: November 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosis of B cell non-Hodgkin's lymphoma

2. Medically stable

3. Able to understand and willingness to sign a written informed consent

4. Able to comply with study procedures

Exclusion Criteria:

1. Previously diagnosed primary immunodeficiency

2. Additional immunosuppressive states

3. Ongoing therapy with Ig replacement

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Secondary Immune Deficiency

Intervention

Drug:
• 20% subcutaneous immunoglobulin
Subcutaneous Immunoglobulin

Locations

Country	Name	City	State
United States	Allergy and Immunology, 222 Alexander Street	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Rochester General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (13)

Cabanillas F, Liboy I, Pavia O, Rivera E. High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication. Ann Oncol. 2006 Sep;17(9):1424-7. — View Citation

Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk. 2013 Apr;13(2):106-11. doi: 10.1016/j.clml.2012.11.011. Epub 2012 Dec 29. — View Citation

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. — View Citation

Cooper N, Arnold DM. The effect of rituximab on humoral and cell mediated immunity and infection in the treatment of autoimmune diseases. Br J Haematol. 2010 Apr;149(1):3-13. doi: 10.1111/j.1365-2141.2010.08076.x. Epub 2010 Feb 11. Review. — View Citation

Davis TA, White CA, Grillo-López AJ, Velásquez WS, Link B, Maloney DG, Dillman RO, Williams ME, Mohrbacher A, Weaver R, Dowden S, Levy R. Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. J Clin Oncol. 1999 Jun;17(6):1851-7. — View Citation

Duraisingham SS, Buckland M, Dempster J, Lorenzo L, Grigoriadou S, Longhurst HJ. Primary vs. secondary antibody deficiency: clinical features and infection outcomes of immunoglobulin replacement. PLoS One. 2014 Jun 27;9(6):e100324. doi: 10.1371/journal.pone.0100324. eCollection 2014. — View Citation

Kaplan B, Kopyltsova Y, Khokhar A, Lam F, Bonagura V. Rituximab and immune deficiency: case series and review of the literature. J Allergy Clin Immunol Pract. 2014 Sep-Oct;2(5):594-600. doi: 10.1016/j.jaip.2014.06.003. Epub 2014 Aug 7. Review. — View Citation

Kelesidis T, Daikos G, Boumpas D, Tsiodras S. Does rituximab increase the incidence of infectious complications? A narrative review. Int J Infect Dis. 2011 Jan;15(1):e2-16. doi: 10.1016/j.ijid.2010.03.025. Epub 2010 Nov 11. Review. — View Citation

Kimby E. Tolerability and safety of rituximab (MabThera). Cancer Treat Rev. 2005 Oct;31(6):456-73. Epub 2005 Jul 28. Review. — View Citation

Makatsori M, Kiani-Alikhan S, Manson AL, Verma N, Leandro M, Gurugama NP, Longhurst HJ, Grigoriadou S, Buckland M, Kanfer E, Hanson S, Ibrahim MA, Grimbacher B, Chee R, Seneviratne SL. Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes. QJM. 2014 Oct;107(10):821-8. doi: 10.1093/qjmed/hcu094. Epub 2014 Apr 28. — View Citation

McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. — View Citation

Spadaro G, Pecoraro A, De Renzo A, Della Pepa R, Genovese A. Intravenous versus subcutaneous immunoglobulin replacement in secondary hypogammaglobulinemia. Clin Immunol. 2016 May;166-167:103-4. doi: 10.1016/j.clim.2016.04.001. Epub 2016 Apr 7. — View Citation

van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of non-neutropenic infections per subject requiring antibiotics in the year after enrollment	How many antibiotics are prescribed in one year for any type of infection	1 year
Secondary	Quality of life score for participants during the one year enrollment	Assessed with Short Form 36 (SF 36)	1 year