Efficacy of Bortezomib (Velcade(R)) in Patients With Advanced Waldenström Macroglobulinemia (WM2)

A Phase IIA Trial Testing the Efficacy of Bortezomib (Velcade(R)) in Patients With Advanced Waldenström Macroglobulinemia

This trial is designed to evaluate the efficacy and toxicity of Bortezomib , an inhibitor of proteasome used in multiple myeloma, in patients with advanced Waldenström's Macroglobulinemia disease.

Study Overview

• Status: Completed
• Conditions: Waldenstrom Macroglobulinemia
• Intervention / Treatment: Drug: BORTEZOMIB

Detailed Description

Open, prospective, multicenter, non controlled phase IIA trial

Primary objectives Evaluation of the efficacy and safety of Velcade in monotherapy for patients with advanced stage Waldenström Macroglobulinemia.

Secondary objectives Evaluation of the activity of the association of High Dose Dexamethasone (HD DXM) with Velcade for patients resistant to Velcade Alone For all patients

• Overall survival
• Safety
• Quality of life
• Duration of response

sample size: With type I error alpha of 5% and type II error beta of 20% and a two-sided test, the number of patients needed in this study is 34 Number of centers: 28 Centers participating to the French cooperative group CLL/WM

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Hôpital La Pitié Salpêtrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

● Established diagnosis of Waldenström macroglobulinemia (the 2nd Workshop on Waldenstrom's macroglobulinemia)

Patient must have had 1 (or 2) lines of chemotherapy containing alkylating agent and/or Fludarabine :and /or monoclonal antibody and must have :

• Life expectancy > 3 months
• Age > 18 years
• ECOG performance status 0-1-2
• ANC > 1 x 109/L
• Creatinine clearance, calculated according to the formula of cockcroft and Gault > 40 ml/min
• Total bilirubin < 2x ULN
• ASAT, ALAT < 2x ULN
• A negative serum pregnancy test one week prior to treatment must be available both for pre-menopausal women and for women who are < 2 years after the onset of menopause
• Adequate contraceptive methods for males and pre-menopausal females for 6 months after treatment discontinuation.
• Written informed consent
• Platelets> 100X 109

Exclusion Criteria:

• Active secondary malignancy or chemotherapy/radiotherapy for any neoplastic disease other than Waldenström macroglobulinemia prior to the study
• Medical condition requiring the long-term (estimated to be more than one month) use of oral corticosteroids
• Patients with active bacterial, viral or fungal infection
• Known infection with HIV, Hepatitis B (except post vaccinal profile) or C
• Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
• Lactation/pregnancy
• Concurrent severe diseases which exclude the administration of therapy heart insufficiency NYHA grade III/IV, LEVF < 50% and or RF < 30%, myocardial infarction within the past 6 months prior to study
• Severe pulmonary or heart problems (acute diffuse pulmonary and pericardial disease)
• Severe chronic obstructive lung disease with hypoxemia
• Severe diabetes mellitus
• Hypertension difficult to control
• Impaired renal function with creatinine clearance < 40 ml/min according to the formula of Cockcroft and Gault
• Cerebral dysfunction
• Richter's syndrome
• Neuropathy> grade 1
• Positive Beta HCG
• Severe Hepato cellular alteration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bortezomib	Drug: BORTEZOMIB; Bortezomib (Velcade(R)): 1.3 mg/m2 on Days 1, 4, 8, and 11 every 21 days for 2 cycles (IV route, push).; For responding patients : up to 6 cycles; For non responding patient : Adjunction of dexamethasone (HD DXM) : 20 mg Days 1,D2, D 4,D 5, D8, D9 and D 11,D12 every 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete and partial remission, defined by the 2nd Workshop on Waldenstrom's macroglobulinemia	3 months and 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of the response	during the study
Overall survival	during the study
Quality of life	months 0, 3, 12, 24

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Véronique LEBLOND, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: October 16, 2008
• First Submitted That Met QC Criteria: October 21, 2008
• First Posted (Estimate): October 22, 2008

Study Record Updates

• Last Update Posted (Estimate): January 18, 2013
• Last Update Submitted That Met QC Criteria: January 17, 2013
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Dexamethasone; Bortezomib; Advanced Waldenström's macroglobulinemia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Waldenstrom Macroglobulinemia; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: P060207