Clinical trial NCT00382694: Fludarabine Added to Induction Treatment in Untreated Multiple Myeloma Patients
Official title: Fludarabine Added to Induction Treatment in Untreated Multiple Myeloma Patients: A Randomised, Placebo Controlled, Double Blind Phase II Trial: NMSG #13/03
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Myeloma
Induction therapy
High-dose melphalan
Autologous stem cell support
Fludarabine
Cyclophosphamide
Dexamethasone
Safety
Toxicity
Lead sponsor: Nordic Myeloma Study Group
Sponsor class: OTHER
First posted: 2006-09-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
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 outcomes:
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.
measure: 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
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Haematology B, Aalborg Hospital, University of Aarhus
city: Herlev
country: Denmark
facility: Department of Haematology, Herlev University Hospital
city: København Ø
country: Denmark
facility: Department of Haematology, Rigshospitalet
city: Odense
country: Denmark
facility: Department of Haematology X, Odense University Hospital
city: Vejle
country: Denmark
facility: Department of Haematology, Vejle Hospital
city: Århus
country: Denmark
facility: Dept. of Haematology, Århus University Hospital
Study officials:
affiliation: Aalborg Univeristy Hospital
name: Hans E. Johnsen, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References: