Comparison of Pharmacokinetics and Pharmacodynamics of Subcutaneous Versus Intravenous Administration of Bortezomib in Patients With Multiple Myeloma

NCT00291538 | Completed Phase 1

• 1 other identifier: BRD/05/9-B
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

In this open-label randomised phase I trial, bortezomib will be administrated to 2 groups of 10 patients with MM who have inclusion criteria use the extended 2nd line indication, either intravenously (group 1 = 10 patients) or subcutaneously (group 2 = 10 patients). The schedule of administration of bortezomib will be the following : 1.3 mg per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles, either IV (group 1) or SC (group 2). The primary objective is to characterize the pharmacokinetics of the 2 routes of administration. The secondary objectives are to characterize the pharmacodynamics (20S proteasome inhibition in whole blood), toxicity, including cardiac safety, and efficacy of the 2 routes of administration.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• characterize the pharmacokinetics of the 2 routes of administration.

Secondary Outcomes (3)

• characterize the pharmacodynamics (20S proteasome inhibition in whole blood),

• toxicity, including cardiac safety,

• efficacy of the 2 routes of administration.

Interventions

bortezomib DRUG

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of MM according to the SWOG criteria (annex I)
• symptomatic MM stage II or III according to Durie-Salmon staging system (annex II) or stage I with one symptomatic osteolytic lesion
• with progressive disease after at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplantation
• with measurable levels of paraprotein in the serum (\> 1g/dl) or in the urine (\> 0.2g/24h)
• age \< 75 years
• able to understand and to given an informed consent
• male, female without childbearing potential or negative urine pregnancy test within 72 hours prior to beginning the treatment. Women of childbearing potential must be following adequate contraceptive measures. Men must agree to use an acceptable method of contraception (for themselves or female partners) for the duration of the study
• no active systemic infection. In the presence of any active systemic infection, adequate broad-spectrum or organism-specific antibiotic coverage must be administered. Patients must be afebrile with stable vital signs while receiving antibiotics for at least 48 hours prior to beginning the treatment with Bortezomib.
• Each subject will weigh ³50 kg and have a body mass index (BMI) of £30 kg/m2 (see annex V for BMI formula).

You may not qualify if:

• life expectancy \< 2 months
• ECOG performance status \> 2 (annex III)
• proven amyloidosis
• positive HIV serology
• antecedents of severe psychiatric disease
• \> NCI grade 2 peripheral neuropathy (Annex IV)
• History of clinically relevant cardiac disease, including prior myocardial infarction, prior or existing heart failure, existing uncontrolled angina or clinically significant pericardial disease Evidence of arrhythmia, 2nd degree or greater AV block or prolonged QTc interval (\>0.45 seconds in males, \>0.47 seconds in females) on screening ECG
• serum biochemical values as follow
• creatinine level \> 200mmol/l
• bilirubin, transaminases or gGT \> 3 the upper normal limit
• potassium, calcium or magnesium outside of upper or lower normal limits
• haematology values as follow
• platelet \< 70x 109 /L within 14 days of enrollment
• absolute neutrophil count \<1.0 x 109/L within 14 days of enrolment
• concomitant use of drugs able to modify QTc interval within 1 week prior to the first dose of bortezomib and during Cycle 1 (Annex VI)

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (3)

Lille UH

Lille, 59000, France

Location

Nancy UH

Nancy, 54000, France

Location

Nantes UH

Nantes, 44093, France

Location

Related Publications (1)

• Moreau P, Coiteux V, Hulin C, Leleu X, van de Velde H, Acharya M, Harousseau JL. Prospective comparison of subcutaneous versus intravenous administration of bortezomib in patients with multiple myeloma. Haematologica. 2008 Dec;93(12):1908-11. doi: 10.3324/haematol.13285. Epub 2008 Sep 2.

  PMID: 18768528 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jean-Luc HAROUSSEAU, MD

  Nantes UH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 10, 2006
• First Posted: February 14, 2006
• Study Start: February 1, 2006
• Primary Completion: June 1, 2007
• Study Completion: October 1, 2008
• Last Updated: February 4, 2009

Record last verified: 2009-02

Locations

FR (3)