Clinical trial NCT01142011: A Study of Belimumab in Treating Symptomatic Waldenstroms Macroglobulinaemia
Official title: A Single Arm, Phase II Study of the Anti-Blys Monoclonal Antibody, Belimumab in Symptomatic Waldenstroms Macroglobulinaemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Symptomatic Waldenstroms Macroglobulinaemia
Keywords: Waldenstroms
Belimumab
anti Blys
monoclonal antibody
Lead sponsor: Cancer Trials Australia
Sponsor class: OTHER
Collaborators: name: Human Genome Sciences Inc.
First posted: 2010-06-11
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. symptomatic anaemia
  2. hyperviscosity symptoms
  3. rapidly rising paraprotein of \>25% or \>5g/l over 3 months
  4. splenomegaly
  5. bulky lymphadenopathy
  6. 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.

Primary outcomes:
measure: Safety of Belimumab infusions in symptomatic WM
timeFrame: Patients are assessed every 28 days while on treatment
Secondary outcomes:
measure: Reduction of IgM paraprotein
timeFrame: Serum Immunoglobulins will be tested every 28 days
measure: Reduction of splenomegaly and/or lymphadenopathy
timeFrame: This will be tested every 28 days
measure: Improvement in anaemia
timeFrame: Patients will be assessed every 28 days while on treatment
measure: Correlate the degree of response with Belimumab levels
timeFrame: Pharmacokinetics will be performed on days 1, 15, 56, 168, 364
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: The Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
Study officials:
affiliation: The Peter MacCallum Cancer Centre
name: David Ritchie
role: PRINCIPAL_INVESTIGATOR
affiliation: The Alfred
name: Andrew Spencer
role: PRINCIPAL_INVESTIGATOR
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