Fludarabine Added to Induction Treatment in Untreated Multiple Myeloma Patients

Fludarabine Added to Induction Treatment in Untreated Multiple Myeloma Patients: A Randomised, Placebo Controlled, Double Blind Phase II Trial: NMSG #13/03

Multiple myeloma is an incurable malignant disease which evnetuelly will relapse after primary treatment. Clonal B-cells have been identified and in theory these cells might be sleeping during primary treatment and be responsible for later relapse. Fluarabine has documented effect on both resting and dividing cells including B-cells. The protocol aim at evaluating safety and toxicity of adding fludarabine to induction chemotherapy with cyclophosphamide and dexamethasone before high-dose melphalan with autologous stem cell support.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Fludarabine

Detailed Description

This is a randomised, placebo controlled, phase II study evaluating toxicity and safety of fludarabine added to CyDex (cyclophosphamide+dexamethasone) as induction therapy in younger patients with untreated and treatment demanding multiple myeloma. The treatment regimen Patients will be randomised at diagnosis either to CyDex + Placebo (control Arm A) or CyDex + Fludarabine (Experimental Arm B).

OBJECTIVES:

• Primary:To determine the toxicity and safety of fludarabine when added to induction therapy by registration of side effects and adverse events in accordance with the common toxicity criteria (CTC).
• Secondary:To quantitate clonal cells in bone marrow and blood by flow cytometry (MRD)and to study new potential prognostic markers identified by cytomic, genomic and proteomic analysis.
• Tertiary: To estimate the efficacy of fludarabine when added to induction chemotherapy(CyDex) in patients with multiple myeloma by clinical end points: disease response and progression free survival.

• Study Type: Interventional
• Enrollment: 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Department of Haematology B, Aalborg Hospital, University of Aarhus
  • Herlev, Denmark, 2730
    • Department of Haematology, Herlev University Hospital
  • København Ø, Denmark, 2100
    • Department of Haematology, Rigshospitalet
  • Odense, Denmark, 5000
    • Department of Haematology X, Odense University Hospital
  • Vejle, Denmark, 7100
    • Department of Haematology, Vejle Hospital
  • Århus, Denmark, 8000
    • Dept. of Haematology, Århus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Multiple myeloma, stage I-III, previously untreated, and eligible for induction therapy followed by high dose treatment supported by autologous stem cell transplantation.

Exclusion Criteria:

• Severe uncontrolled clinical or microbiological evidence of infection at the time of enrolment.
• Other active malignancy.
• Severe coincident heart or lung disease including uncontrolled hypertension, unstable angina, congestive heart failure, coronary angioplasty within six months, myocardial infarction within the last six months, or uncontrolled cardiac arrhythmia.
• Other severe illness including poorly controlled diabetes.
• Haemolytic anaemia (Coombs positive without evidence of haemolysis is accepted).
• Idiopathic thrombocytopenic purpura.
• Terminal illness.
• Allogenic transplantation planned within 6 months.
• Chemotherapy before inclusion.
• Pregnancy or breast-feeding, or inadequate contraceptive precautions.
• Psychiatric disease, abuse of alcohol or narcotics, or any other disorder that might compromise the patients ability to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The toxicity and safety of Fludarabine when added to induction therapy by registration of side effects and adverse events in accordance with the common toxicity criteria (CTC).

Secondary Outcome Measures

Outcome Measure
Quantification of clonal cells in bone marrow and blood by flow cytometry (MRD) and to study new potential prognostic markers identified by cytomic, genomic and proteomic analysis.
Estimation of the efficacy of Fludarabine when added to induction chemotherapy (CyDex) in patients with multiple myeloma by clinical end points: disease response and progression free survival

Collaborators and Investigators

• Sponsor: Nordic Myeloma Study Group
• Investigators: Principal Investigator: Hans E. Johnsen, Prof., MD, Aalborg Univeristy Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Study Completion: December 1, 2006

Study Registration Dates

• First Submitted: September 28, 2006
• First Submitted That Met QC Criteria: September 28, 2006
• First Posted (Estimate): September 29, 2006

Study Record Updates

• Last Update Posted (Estimate): September 29, 2006
• Last Update Submitted That Met QC Criteria: September 28, 2006
• Last Verified: September 1, 2006

More Information

Terms related to this study

• Keywords: Safety; Cyclophosphamide; Dexamethasone; Toxicity; Myeloma; Fludarabine; Induction therapy; High-dose melphalan; Autologous stem cell support
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Fludarabine
• Other Study ID Numbers: NMSG#13/03