Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse

Study Overview
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Brief Summary
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Assessment of the antitumour effect of zoledronic acid in patients with multiple myeloma and asymptomatic biochemical relapse It´s proposed to investigate the use of Zoledronic acid as single therapy in patients with Multiple Myeloma in biochemical relapse. The following must be noted: Patients with no formal indication for chemotherapy treatment will be included, as patients with symptomatic myeloma who after responding show biochemical relapse are generally not treated. This allows for generating both a group of patients untreated, on no additional treatment and a treatment group on zoledronic acid. As these are relapsing symptomatic patients, their number is far higher than patients with quiescent Multiple Myeloma. This allows for expecting a good enrolment. There are few reliable data on symptom progression after biochemical relapse, though it is one of the new objectives occurring in almost all clinical trials on myeloma. In the VISTA study, it has been estimated that the median time to the new treatment is 5 months (combining progression-free time and time to the next treatment). This time is much shorter than the median quiescent myeloma progression-free survival, so a very long follow-up time will not be necessary in this patient group. The administration of this drug to these patients can help prevent skeleton-related complications in the future, the study of which will be a secondary objective of this study.

Detailed Description
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Zometa is administrated every 4 weeks at dose of 4 mg. The limit of administrations is 12. The first infusion is in the visit 2 and the last is in visit 13

Official Title
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Assessment of the Antitumour Effect of Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse: Prospective Clinical Trial of the GEM/PETHEMA Group

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: zoledronic acid
* Other: No treatment control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged ≥18 years. Signed informed consent before performing any study procedure that is not the part of the regular medical care of the patients. Diagnosis of MM, with biochemical relapse after initial response with no symptoms resulting from the disease (CRAB), defined as a re-positivation of a previous immunofixation (two samples) or increase above 25% of serum or urine protein M. In the investigator's opinion, ability to meet all clinical trial requirements Exclusion Criteria: Treatment with bisphosphonates (oral route and/or endovenous route) within 3 months prior to inclusion. Treatment with denosumab within three months prior to inclusion. Criteria of symptomatic disease or organic damage related to disease, defined as: Impaired renal function: serum creatinine >2 mg/dl or 173 mmol/l. Calcium increase: serum calcium ≥12 mg/dl within 28 days prior to inclusion. Anaemia: haemoglobin < 10 g/dl or 2 g/dl below normal ranges. Bone injury: new osteolytic lesions (from diagnosis) seen within 3 months prior to inclusion, current pathological fractures or increase of osteopenia (from diagnosis) in bone radiology series. Others: amyloidosis with current organic damage, recurrent bacterial infections (more than 2 events in 12 months), symptomatic hyperviscosity, presence of plasmacytomas. Patients with current and active dental disorders (dental, jaw infection, bone exposed in the mouth, jaw osteonecrosis). Patients developing jaw osteonecrosis or other serious adverse events due to treatment with any bisphosphonate . Significant liver disease: Bilirubin > 3 g/dl. ALT > 2.5 x the upper limit of normal AST > 2.5 x the upper limit of normal Patients who are currently in another clinical trial or receiving any investigational agent. Pregnancy or nursing. Parathyroid gland diseases. Previous malignancy with a high risk of death or bone disease: breast cancer, prostate cancer or lung cancer, even if on complete response. Active presence of neoplasms other than Multiple Myeloma

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoledronate acid<br> | Drug: zoledronic acid<br>* Zoledronic acid 4 mg every 4 weeks for a total of 12 treatments<br>|
| Other: No treatment control<br> | Other: No treatment control<br>* Patients doesn't receive treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to next need treatment | Time to the next treatment, considered as the time from the randomization date to the start of the next chemotherapy treatment for Multiple Mieloma or death for any cause | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to symptom relapse | Time to symptom relapse, considered as the time from randomization to symptom relapse | 1 year | 
| disease progression | To describe the differences between patients treated with ZOL or not in terms of type of disease progression (bone and extra-bone). | 2 years | 
| prognostic factors | To describe the prognostic factors in patients with MM and asymptomatic biochemical relapse | 2 years | 
| antitumour effect of ZOL | To assess the antitumour effect of ZOL on other clinically significant parameters in MM, including tumour response to ZOL | 1 year | 
| Overall survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Zoledronic acid