Clinical trial NCT01087008: Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Zoledronic acid
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
Collaborators: name: Dynamic Solutions
name: Novartis
First posted: 2010-03-15
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Time to next need treatment
timeFrame: 6 months
Secondary outcomes:
measure: Time to symptom relapse
timeFrame: 1 year
measure: disease progression
timeFrame: 2 years
measure: prognostic factors
timeFrame: 2 years
measure: antitumour effect of ZOL
timeFrame: 1 year
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebrón
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Murcia
country: Spain
facility: Hospital Jose María Morales Meseguer
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Dureta
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Tenerife
country: Spain
facility: Hospital Universitario de Canarias
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset.
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: Hospital Clínico Lozano Blesa
Study officials:
affiliation: PETHEMA Foundation
name: García Sanz Ramon, Dr
role: STUDY_CHAIR
References:
citation: R. García-Sanz, A. Oriol, J. de la Rubia, L. Palomera, P. Ribas, MT. Hernández, MJ. Moreno, J. Bargay, A. Ramírez, AI. Teruel, MJ. Blanchard, M. Gironella, M. Granell, E. Abellá, MA Sampol, R. Martínez, JF San Miguel EVALUTION OF BENEFITS AND POTENTIAL ANTIMYELOMA EFFECT OF ZOLEDRONIC ACID IN PATIENTS WITH ASYMPTOMATIC BIOCHEMICAL RELAPSES. Abstract for ASH 2012
citation: R. García-Sanz, A. Oriol, J. de la Rubia, L. Palomera, P. Ribas, MT. Hernández, MJ. Moreno, J. Bargay, A. Ramírez, AI. Teruel, MJ. Blanchard, M. Gironella, M. Granell, E. Abellá, MA Sampol, R. Martínez, JF San Miguel EVALUTION OF BENEFITS AND POTENTIAL ANTIMYELOMA EFFECT OF ZOLEDRONIC ACID IN PATIENTS WITH ASYMPTOMATIC BIOCHEMICAL RELAPSES. Abstract for EHA 2012
citation: R. García-Sanz, A. Oriol, J. de la Rubia, L. Palomera, P. Ribas, MT. Hernández, MJ. Moreno, J. Bargay, A. Ramírez, AI. Teruel, MJ. Blanchard, M. Gironella, M. Granell, E. Abellá, MA Sampol, R. Martínez, JF San Miguel EVALUTION OF BENEFITS AND POTENTIAL ANTIMYELOMA EFFECT OF ZOLEDRONIC ACID IN PATIENTS WITH ASYMPTOMATIC BIOCHEMICAL RELAPSES. Poster for EHA 2012
citation: Garcia-Sanz R, Oriol A, Moreno MJ, de la Rubia J, Payer AR, Hernandez MT, Palomera L, Teruel AI, Blanchard MJ, Gironella M, Ribas P, Bargay J, Abella E, Granell M, Ocio EM, Ribera JM, San Miguel JF, Mateos MV; Spanish Myeloma Group (GEM/PETHEMA). Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial. Haematologica. 2015 Sep;100(9):1207-13. doi: 10.3324/haematol.2015.128439. Epub 2015 Jun 11.