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89Zr-bevacizumab PET Scan in Patients With Relapsing Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01859234
Recruitment Status : Unknown
Verified May 2013 by E.G.M. de Waal, University Medical Center Groningen.
Recruitment status was:  Recruiting
First Posted : May 21, 2013
Last Update Posted : May 21, 2013
Sponsor:
Information provided by (Responsible Party):
E.G.M. de Waal, University Medical Center Groningen

Brief Summary:
The purpose of this study is to see whether 89Zr-bevacizumab PET scanning is feasible in relapsing multiple myeloma patients.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: 89Zr-bevacizumab Not Applicable

Detailed Description:

Multiple Myeloma (MM) is a clonal B cell disorder characterised by a monoclonal plasma cell population in bone marrow, with bone pain, anaemia, hypercalcaemia, and kidney dysfunction as clinically presenting symptoms. Osseous involvement is one of the most predominant features of patients with MM; 90% of the patients develop lytic bone lesions. Lytic bone lesions are the result of increased bone resorption and reduced bone formation. The regular method to detect bone lesions is skeletal survey. This technique can only detect lesions that have lost 30% or more of the trabecular bone. Another weakness is the fact that lesions persist after treatment with chemotherapy or radiotherapy and no clear distinction can be made whether vital tumour cells persist in these lesions. New bone lesions are a sign of disease progression. Furthermore they give clinical signs as bone pain and in the worse case scenario pathological fractures. Alternative scanning methods have been developed to visualize the malignant plasma for example by making use of enhanced metabolic activity of the plasma cells defined by the uptake of 18F-fluorodeoxyglucose -Positron Emission tomography (FDG-PET. The use of FDG-PET in newly diagnosed MM patients is well studied.

The increased FDG-uptake by the tumour is related to a high metabolic activity. This might be a consequence of tumour hypoxia causing new vessel formation. There seems to be a relationship between MM and angiogenesis, the formation of new blood vessels from exciting blood vessels. There is an increased microvessel density (MVD) of the affected bone marrow in patients with active MM. Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. MM cell lines were found to express VEGF mRNA and secrete the protein in the extracellular environment thereby stimulating angiogenesis.

Inhibition of the process of angiogenesis is used in the treatment of MM, for instance by means of thalidomide and lenalidomide. Blocking VEGF itself can be obtained by means of bevacizumab, a recombinant, humanised monoclonal antibody that binds to all isoforms of human VEGF with high affinity. Treatment with bevacizumab is well established in solid tumours, like colon cancers and renal cell carcinomas and is currently tested in acute myeloid leukaemia and MM.

VEGF imaging with radiolabeled bevacizumab has been developed. Bevacizumab binds VEGF and can be labeled with the PET isotope Zirconium-89 (89Zr) while preserving VEGF binding properties. In a human ovarian tumor xenograft, PET imaging 24 hours after injection of 89Zr-bevacizumab showed high uptake in well perfused organs and in the tumor.

The high VEGF production by myeloma cells makes VEGF a very interesting target for tumor visualization. 89Zr-bevacizumab PET imaging could be more sensitive for myeloma lesions.

So, in conclusion, VEGF is expressed by MM plasma cells, thereby providing a rationale that the assessment of VEGF-levels in the micro-environment of MM tumors could potentially be used as a diagnostic tool to see if there is disease activity. Especially in the relapsed setting this is of invaluable importance, since conventional skeletal survey has limitations in this setting. Furthermore, 89Zr-bevacizumab PET imaging could provide information about treatment options and treatment response.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Evaluation of VEGF Expression With 89Zr-bevacizumab PET Scan in Patients With Relapsing Multiple Myeloma; a Feasibility Study
Study Start Date : May 2013
Estimated Primary Completion Date : May 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: 89Zr-bevacizumab PET scan
all patients included in the study will have a 89Zr-bevacizumab PET scan
Drug: 89Zr-bevacizumab
89Zr-bevacizumab will only be given once, prior for the PET scan. 5 mg will be given iv.
Other Names:
  • Bevacizumab Roche registration limited eu/1/04/300/001
  • 89Zr-bevacizumab ATC code L01XC07




Primary Outcome Measures :
  1. Focal lesion of 89Zr-bevacizumab PET scanning in patients with relapsing multiple myeloma [ Time Frame: during scanning ]
    We assume focal lesion will be feasible with 89Zr-bevacizumab PET scanning in patients with relapsing multiple myeloma. For each 89Zr-bevacizumab PET scan the amount of focal lesion and the localisation will be reported. When there is diffuse bone marrow uptake this will also be reported. The focal lesion found on the 89Zr-bevacizumab PET scan will be compared with focal lesions found on the FDG-PET scan. Furthermore the amount of focal lesion will be compared with the expression of VEGF, MVD, HIF 1 alpha and 2 alpha and GLUT 1 and 3.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with relapsing multiple myeloma according to international defined guidelines:

Relapse after having achieved complete remission:

  1. Reappearance of paraprotein
  2. More than 5% plasma cells in bone marrow.
  3. New lytic lesions or progression of old lesions.
  4. New hypercalcaeamia.

Relapse after having achieved partial remission

  1. Increases of paraprotein with more than 25%
  2. Increase of urine paraprotein with more than 25%
  3. Increase of plasma cells in bone marrow with 10%
  4. New lytic lesions or progression of old lesions
  5. New hypercalcaemia -

Exclusion Criteria:

Radiotherapy in the last 3 months.

  • Ineligible to lay supine during the PET scan.
  • Age ≤18 years.
  • Pregnancy.
  • Claustrophobia
  • Severe kidney dysfunction; serum-creatinine ≥250 µM

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01859234


Contacts
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Contact: E G de Waal, MD +31503612354 e.g.m.de.waal@umcg.nl
Contact: E vellenga, PhD/MD +31503612354 e.vellenga@umcg.nl

Locations
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Netherlands
UMCG Recruiting
Groningen, Netherlands, 9713GZ
Contact: E G de Waal, MD    +31503612354    e.g.m.de.waal@umcg.nl   
Principal Investigator: E G de Waal, MD         
Sponsors and Collaborators
University Medical Center Groningen

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Responsible Party: E.G.M. de Waal, Hematologist, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT01859234     History of Changes
Other Study ID Numbers: UMCGABR40641
First Posted: May 21, 2013    Key Record Dates
Last Update Posted: May 21, 2013
Last Verified: May 2013

Keywords provided by E.G.M. de Waal, University Medical Center Groningen:
multiple myeloma
PET scan

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bevacizumab
89Zr-bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action