NCT01142011

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
15

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2009

Typical duration for phase_2

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2009

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

June 10, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 11, 2010

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2013

Completed
Last Updated

February 10, 2012

Status Verified

February 1, 2012

Enrollment Period

2.6 years

First QC Date

June 10, 2010

Last Update Submit

February 8, 2012

Conditions

Symptomatic Waldenstroms Macroglobulinaemia

Keywords

WaldenstromsBelimumabanti Blysmonoclonal antibody

Outcome Measures

Primary Outcomes (1)

  • Safety of Belimumab infusions in symptomatic WM

    Patients are assessed every 28 days while on treatment

Secondary Outcomes (4)

  • 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

Study Arms (1)

Belimumab

EXPERIMENTAL

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

Interventions

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.

Belimumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +2 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

The Peter MacCallum Cancer Centre

Melbourne, Victoria, 3002, Australia

RECRUITING

Alfred Health

Melbourne, Victoria, 3181, Australia

RECRUITING

Related Publications (22)

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    PMID: 11407690BACKGROUND

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  • 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.

    PMID: 18786258BACKGROUND

  • 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.

    PMID: 11520463BACKGROUND

  • 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.

    PMID: 10801128BACKGROUND

  • 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.

    PMID: 16517838BACKGROUND

  • 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.

    PMID: 16640813BACKGROUND

  • 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.

    PMID: 10587360BACKGROUND

  • 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.

    PMID: 18668552BACKGROUND

  • 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.

    PMID: 11104810BACKGROUND

  • 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.

    PMID: 15358625BACKGROUND

  • 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.

    PMID: 12566413BACKGROUND

  • 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.

    PMID: 11509691BACKGROUND

  • 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.

    PMID: 11733583BACKGROUND

  • 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.

    PMID: 10881172BACKGROUND

  • Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, Guo J, Stolina M, Boyle WJ, Sarosi I, Hsu H, Senaldi G, Theill LE. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol. 2000 Sep;1(3):252-6. doi: 10.1038/79802.

    PMID: 10973284BACKGROUND

  • Zhang J, Roschke V, Baker KP, Wang Z, Alarcon GS, Fessler BJ, Bastian H, Kimberly RP, Zhou T. Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol. 2001 Jan 1;166(1):6-10. doi: 10.4049/jimmunol.166.1.6.

    PMID: 11123269BACKGROUND

  • Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001 Feb 23;104(4):487-501. doi: 10.1016/s0092-8674(01)00237-9. No abstract available.

    PMID: 11239407BACKGROUND

  • Mackay F, Schneider P, Rennert P, Browning J. BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003;21:231-64. doi: 10.1146/annurev.immunol.21.120601.141152. Epub 2001 Dec 19.

    PMID: 12427767BACKGROUND

  • Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, Hession C, Schneider P, Sizing ID, Mullen C, Strauch K, Zafari M, Benjamin CD, Tschopp J, Browning JL, Ambrose C. BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science. 2001 Sep 14;293(5537):2108-11. doi: 10.1126/science.1061965. Epub 2001 Aug 16.

    PMID: 11509692BACKGROUND

  • Yan M, Wang H, Chan B, Roose-Girma M, Erickson S, Baker T, Tumas D, Grewal IS, Dixit VM. Activation and accumulation of B cells in TACI-deficient mice. Nat Immunol. 2001 Jul;2(7):638-43. doi: 10.1038/89790.

    PMID: 11429549BACKGROUND

  • Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, Li Y, Galperina O, Giri J, Roschke V, Nardelli B, Carrell J, Sosnovtseva S, Greenfield W, Ruben SM, Olsen HS, Fikes J, Hilbert DM. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999 Jul 9;285(5425):260-3. doi: 10.1126/science.285.5425.260.

    PMID: 10398604RESULT

MeSH Terms

Interventions

belimumab

Study Officials

  • David Ritchie

    The Peter MacCallum Cancer Centre

    PRINCIPAL INVESTIGATOR

  • Andrew Spencer

    The Alfred

    PRINCIPAL INVESTIGATOR

Central Study Contacts

David Ritchie Ritchie

CONTACT

+61396561111david.ritchie@petermac.org

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 10, 2010

First Posted

June 11, 2010

Study Start

November 1, 2009

Primary Completion

June 1, 2012

Study Completion

January 1, 2013

Last Updated

February 10, 2012

Record last verified: 2012-02

Locations

AU(2)