Trial Information

Stage I Multiple Myeloma Treatment

RATIONAL:

Multiple Myeloma in spite of therapy progresses mainly due to stem cell auto transplant,
still remain a deadly disease. About 2000 new cases are diagnosed every year in France. The
asymptomatic Stage I MM according to Duries and Salmon's staging are usually only watch over
and only treated at progression. Zoledronate is a third generation aminobiphosphonate (BP),
probably the most powerful among the available compounds which received market clearance
authorisation in MM with bone damage. During MM, bone's hyper resorption is premature.
Interactions exist between tumor growth and bone lyses. Zoledronate's got a proper
antimyeloma's action (induce plasma cells apoptosis). We propose to test the early use of
Zoledronate as soon as stage I MM to delay progression.

STUDY'S OBJECTIVES:

- PRINCIPAL: Assessment of survival without progression stage I MM in two groups: A arm:
simple survey and B arm: administration of BP.

- SECONDARY: Describe different progression's type noticed (bone/extra bone) and define
the prognosis factor of a fast stage I MM evolution (standard factors, cytogenetic 13
deletion, bone's restructuring strains: crosslaps, bone alkaline phosphatase), list
side effects.

STUDY'S KIND:

Multicenter international randomised trial, open labelled, with individual profit.

CONTRIBUTING CENTERS:

Intergroupe Francophone du Myélome's centers.

INCLUSIONS CRITERIA:

Asymptomatic stage I MM without bone's lesion on the standard radiographs.

STUDY'S MONITORING:

After checking inclusion and non inclusion specifications, the patient will be included in
the study and randomized (A arm or B arm) before all treatment. The randomisation will be
done by center and stratified according to the diagnostic date witch a year or not.

- Arm A: simple survey as standard practice.

- Arm B: a 15 minutes infusion of Zoledronate every month until progression or a maximum
of 18 infusions if no progression. The exams are the one usually defined according to
good clinical practices guidelines besides cytogenetic, bone's restructuring strain and
serum creatin dosage before each infusion in B arm.

STATISTICAL PURPOSES:

The minimum number of patients required showing a median survival time increase without
progression of 26 months in the control arm and 38 months in the BP arm is about 175
patients in each arm for a 48 months inclusion's period, and a monitoring of 24 months after
the last inclusion (i.e. a study's length of 6 years).