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Symptomatic Waldenstroms MacroglobulinaemiaPhase 2NCT01142011

A Study of Belimumab in Treating Symptomatic Waldenstroms Macroglobulinaemia

A Phase 2 study testing Belimumab in people with Symptomatic Waldenstroms Macroglobulinaemia, run by Cancer Trials Australia at 2 sites in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Belimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesAustralia
Study dates
Nov 2009to Jan 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 17Show fewer
  • 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

Who cannot join

  • 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).
Show all 13Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

David Ritchie Ritchie contact

+61396561111

david.ritchie@petermac.org

Australia2 sites, 2 recruiting

  • The Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3002

    David Ritchie

    Recruiting

  • Alfred Health

    Melbourne, Victoria, 3181

    Andrew Spencer, +61390762000, aspencer@netspace.net.au

    Andrew Spencer

    Recruiting

Other trials in Australia

About this study

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

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.

Being tested
Belimumab
Keywords
Waldenstroms, Belimumab, anti Blys, monoclonal antibody

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelimumabDrug

    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.

Study groups in NCT01142011
Study groupRoleWhat they receive
BelimumabExperimentalThe 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).
Receives: Drug: Belimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of Belimumab infusions in symptomatic WM

    Measured: Patients are assessed every 28 days while on treatment

Secondary outcomes (4)

  1. Reduction of IgM paraprotein

    Measured: Serum Immunoglobulins will be tested every 28 days

  2. Reduction of splenomegaly and/or lymphadenopathy

    Measured: This will be tested every 28 days

  3. Improvement in anaemia

    Measured: Patients will be assessed every 28 days while on treatment

  4. Correlate the degree of response with Belimumab levels

    Measured: Pharmacokinetics will be performed on days 1, 15, 56, 168, 364

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2010 (estimated)
  2. Study startNov 2009
  3. Primary completionJun 2012 (estimated)
  4. Study completionJan 2013 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01142011
Sponsor's protocol ID
HGSI Belimumab in WM
Status last verified
Feb 2012
First submitted
10 Jun 2010
Last updated
10 Feb 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001 Jun;44(6):1313-9. doi: 10.1002/1529-0131(200106)44:63.0.CO;2-S.

    PubMed 11407690

  • Elsawa SF, Novak AJ, Grote DM, Ziesmer SC, Witzig TE, Kyle RA, Dillon SR, Harder B, Gross JA, Ansell SM. B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenstrom macroglobulinemia. Blood. 2006 Apr 1;107(7):2882-8. doi: 10.1182/blood-2005-09-3552. Epub 2005 Nov 22.

    PubMed 16304043

  • Furie R, Stohl W, Ginzler EM, Becker M, Mishra N, Chatham W, Merrill JT, Weinstein A, McCune WJ, Zhong J, Cai W, Freimuth W; Belimumab Study Group. Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus. Arthritis Res Ther. 2008;10(5):R109. doi: 10.1186/ar2506. Epub 2008 Sep 11.

    PubMed 18786258

  • Gross JA, Dillon SR, Mudri S, Johnston J, Littau A, Roque R, Rixon M, Schou O, Foley KP, Haugen H, McMillen S, Waggie K, Schreckhise RW, Shoemaker K, Vu T, Moore M, Grossman A, Clegg CH. TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS. Immunity. 2001 Aug;15(2):289-302. doi: 10.1016/s1074-7613(01)00183-2.

    PubMed 11520463

  • Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000 Apr 27;404(6781):995-9. doi: 10.1038/35010115.

    PubMed 10801128

  • Halpern WG, Lappin P, Zanardi T, Cai W, Corcoran M, Zhong J, Baker KP. Chronic administration of belimumab, a BLyS antagonist, decreases tissue and peripheral blood B-lymphocyte populations in cynomolgus monkeys: pharmacokinetic, pharmacodynamic, and toxicologic effects. Toxicol Sci. 2006 Jun;91(2):586-99. doi: 10.1093/toxsci/kfj148. Epub 2006 Mar 3.

    PubMed 16517838

  • Kimby E, Treon SP, Anagnostopoulos A, Dimopoulos M, Garcia-Sanz R, Gertz MA, Johnson S, LeBlond V, Fermand JP, Maloney DG, Merlini G, Morel P, Morra E, Nichols G, Ocio EM, Owen R, Stone M, Blade J. Update on recommendations for assessing response from the Third International Workshop on Waldenstrom's Macroglobulinemia. Clin Lymphoma Myeloma. 2006 Mar;6(5):380-3. doi: 10.3816/CLM.2006.n.013.

    PubMed 16640813

  • Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999 Dec 6;190(11):1697-710. doi: 10.1084/jem.190.11.1697.

    PubMed 10587360

  • Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, Recta V, Zhong J, Freimuth W. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008 Aug;58(8):2453-9. doi: 10.1002/art.23678.

    PubMed 18668552

  • Rennert P, Schneider P, Cachero TG, Thompson J, Trabach L, Hertig S, Holler N, Qian F, Mullen C, Strauch K, Browning JL, Ambrose C, Tschopp J. A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth. J Exp Med. 2000 Dec 4;192(11):1677-84. doi: 10.1084/jem.192.11.1677.

    PubMed 11104810

  • Scapini P, Carletto A, Nardelli B, Calzetti F, Roschke V, Merigo F, Tamassia N, Pieropan S, Biasi D, Sbarbati A, Sozzani S, Bambara L, Cassatella MA. Proinflammatory mediators elicit secretion of the intracellular B-lymphocyte stimulator pool (BLyS) that is stored in activated neutrophils: implications for inflammatory diseases. Blood. 2005 Jan 15;105(2):830-7. doi: 10.1182/blood-2004-02-0564. Epub 2004 Sep 9.

    PubMed 15358625

  • Scapini P, Nardelli B, Nadali G, Calzetti F, Pizzolo G, Montecucco C, Cassatella MA. G-CSF-stimulated neutrophils are a prominent source of functional BLyS. J Exp Med. 2003 Feb 3;197(3):297-302. doi: 10.1084/jem.20021343.

    PubMed 12566413

  • Schiemann B, Gommerman JL, Vora K, Cachero TG, Shulga-Morskaya S, Dobles M, Frew E, Scott ML. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 2001 Sep 14;293(5537):2111-4. doi: 10.1126/science.1061964. Epub 2001 Aug 16.

    PubMed 11509691

  • Schneider P, Takatsuka H, Wilson A, Mackay F, Tardivel A, Lens S, Cachero TG, Finke D, Beermann F, Tschopp J. Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen. J Exp Med. 2001 Dec 3;194(11):1691-7. doi: 10.1084/jem.194.11.1691.

    PubMed 11733583

  • Yan M, Marsters SA, Grewal IS, Wang H, Ashkenazi A, Dixit VM. Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity. Nat Immunol. 2000 Jul;1(1):37-41. doi: 10.1038/76889.

    PubMed 10881172

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Belimumab in people with Symptomatic Waldenstroms Macroglobulinaemia, run by Cancer Trials Australia at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 10 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact David Ritchie Ritchie (+61396561111, david.ritchie@petermac.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of Belimumab infusions in symptomatic WM (time frame: Patients are assessed every 28 days while on treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01142011, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2012.

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