A Study of Belimumab in Treating Symptomatic Waldenstroms Macroglobulinaemia

Study Overview
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Brief Summary
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Hypothesis; That inhibition of plasma Blys by the monoclonal antibody Belimumab will reduce both the survival of the lymphoplasmacytoid cells of Waldenstrom Macroglobulinaemia (WM), and their production of monoclonal IgM, resulting in a reduction of IgM paraprotein.

Official Title
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A Single Arm, Phase II Study of the Anti-Blys Monoclonal Antibody, Belimumab in Symptomatic Waldenstroms Macroglobulinaemia

Conditions
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Symptomatic Waldenstroms Macroglobulinaemia

Intervention / Treatment
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* Drug: Belimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age. Diagnosis of WM histologically confirmed on bone marrow biopsy. Detectable IgM paraprotein >5 g/L Less than 3 lines of prior therapy for WM Full blood count within 4 weeks prior to screening shows ANC >1.0 x109/l AND platelet count >50 x109/l Therapy indicated due to development of one or more of the following: symptomatic anaemia hyperviscosity symptoms rapidly rising paraprotein of >25% or >5g/l over 3 months splenomegaly bulky lymphadenopathy B symptoms or paraneoplastic phenomena, which, in the opinion of the investigator are the result of progressive WM. Life expectancy >12 months ECOG < 3 Able to provide informed consent Ability to understand the requirements of the study, provide written informed consent, including consent for the use and disclosure of research-related health information, and comply with the protocol procedures, including required study visits. Subjects of child bearing potential must agree to use effective contraception throughout the study and for 3 months after the last dose of belimumab Exclusion Criteria: Prior therapy with belimumab. Pregnant or breast feeding Chemotherapy, immunotherapy or biological therapy within 4 weeks of enrolment. Therapeutic plasma exchange can continue- see section 3.1.4. Creatinine clearance (calculated by Cockcroft-Gault) < 60ml/min Bilirubin >2x ULN, ALT >2x ULN. History of an allergic or anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies, a history of severe allergic reaction to drugs, food, or insects requiring medical intervention, or a history of hypersensitive triad (having all 3 features of allergic rhinitis with nasal polyps, asthma, and aspirin sensitivity). Prior opportunistic infection including tuberculosis or atypical mycobacterial infection, multi-dermatome Herpes Zoster or Pneumocystis pneumonia or invasive fungal infection (not including oral or vaginal candidiasis or superficial dermatophytes) . Active infection with hepatitis B, hepatitis C or HIV or historically positive test or test positive at screening for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody. History of organ transplant (eg, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. Planned surgical procedure during the treatment period of this study or a history of any other medical disease (eg, cardiopulmonary), laboratory abnormality, or condition that, in the opinion of the principal investigator, makes the subject unsuitable for the study. Hospitalization for treatment of infection within 60 days of Day 1. Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of Day 1. Current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 1.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belimumab<br>The first cycle of Belimumab is a loading cycle of 3 doses over 28 days (days 1, 15, 29). After the first cycle, additional cycles of belimumab will be administered every 28 ± 1 days (cycle 2 and all subsequent cycles). | Drug: Belimumab<br>* The first cycle of Belimumab (10mg/kg by intravenous (IV) infusion) is a loading cycle of 3 doses over 28 days (days 1, 15, 29). After the first cycle, additional cycles of belimumab (10mg/kg by intravenous (IV) infusion) will be administered every 28 ± 1 days (cycle 2 and all subsequent cycles). The infusion will be administered over a minimum period of 1 hour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Belimumab infusions in symptomatic WM |  | Patients are assessed every 28 days while on treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of IgM paraprotein |  | Serum Immunoglobulins will be tested every 28 days | 
| Reduction of splenomegaly and/or lymphadenopathy |  | This will be tested every 28 days | 
| Improvement in anaemia |  | Patients will be assessed every 28 days while on treatment | 
| Correlate the degree of response with Belimumab levels |  | Pharmacokinetics will be performed on days 1, 15, 56, 168, 364 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waldenstroms, Belimumab, anti Blys, monoclonal antibody