A Study of Belimumab in Treating Symptomatic Waldenstroms Macroglobulinaemia

NCT ID: NCT01142011

Last Updated: 2012-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-30

Study Completion Date

2013-01-31

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.

Detailed Description

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Conditions

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Symptomatic Waldenstroms Macroglobulinaemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Belimumab

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).

Group Type EXPERIMENTAL

Belimumab

Intervention Type DRUG

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.

Interventions

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Belimumab

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.

Intervention Type DRUG

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:

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Human Genome Sciences Inc.

INDUSTRY

Sponsor Role collaborator

Cancer Trials Australia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Ritchie

Role: PRINCIPAL_INVESTIGATOR

The Peter MacCallum Cancer Centre

Andrew Spencer

Role: PRINCIPAL_INVESTIGATOR

The Alfred

Locations

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The Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Alfred Health

Melbourne, Victoria, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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David Ritchie Ritchie

Role: CONTACT

+61396561111

Facility Contacts

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Andrew Spencer

Role: primary

+61390762000

References

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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.

Reference Type BACKGROUND
PMID: 11407690 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16304043 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18786258 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11520463 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10801128 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16517838 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16640813 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10587360 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18668552 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11104810 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15358625 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12566413 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11509691 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11733583 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10881172 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10973284 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11123269 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11239407 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12427767 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11509692 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11429549 (View on PubMed)

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.

Reference Type RESULT
PMID: 10398604 (View on PubMed)

Other Identifiers

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HGSI Belimumab in WM

Identifier Type: -

Identifier Source: org_study_id

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