Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Effect of i.v. Bisphosphonate on Health-Related Quality of Life and Skeletal Morbidity for Newly Diagnosed Treatment Demanding Multiple Myeloma. A Prospective Randomised Double Blinded Dose-Effective Study With Cost-Utility Analysis.
Brief Summary: Multiple myeloma is a malignant hematological disease dominated by monoclonal plasma cells in the bone marrow. Major symptoms are related to the bones due to an increased bone resorption and a decreased bone formation leading to bone pain and increased risk of fractures. The normal osteoclasts are responsible for bone degradation through stimulation from the malignant plasma cells. Bisphosphonates have been shown to inhibit the osteoclast activity but may have serious side-effects due to renal toxicity and the optimal dose have not been established.

In a randomized double blinded design it is aim to compare the standard of monthly injections of 90 mg pamidronate with 30 mg.

The primary end-point is physical function estimated by EORTC QLQ-C30 questionnaire at 12 months after starting the treatment in newly diagnosed treatment demanding multiple myeloma. Secondary end-points are skeletal related events, cost-utility analysis, response, response duration and survival and quality of life with respect to fatigue and pain.


Options:
A: 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
B: Inclusion Criteria:

* Adults with histologically or cytologically confirmed breast adenocarcinoma
* radiographic evidence of at least one bone mets
* Easter Cooperative Oncology Group status of 0, 1 or 2;
* adequate organ function

Exclusion Criteria:

* Current or prior IV bisphosphonate administration
* current or prior oral bisphosphonates for bone mets
* life expectancy of less than 6 months
C: Inclusion Criteria:

* New diagnosed multiple myeloma with treatment demanding disease

Exclusion Criteria:

* Life-expectancy less than 3 months, another active malignant disease, treatment with bisphosphonates for more than 3 months within the last 6 months, patients with creatinine above 400 µmol/l 4 weeks after starting chemotherapy, patients who cannot cooperate for monthly infusions, patients who do not give their informed consent
D: DISEASE CHARACTERISTICS:

* Diagnosis of multiple myeloma (MM)

  * Previously untreated asymptomatic disease
  * No requirement for immediate chemotherapy for active MM, such as hypercalcemia from myeloma or painful bone lesions
* No solitary plasmacytoma
* Measurable or evaluable disease as defined by one of the following:

  * Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
  * More than 200 mg of monoclonal protein in the urine by 24-hour electrophoresis
  * Measurable soft tissue plasmacytoma by physical exam with ruler or by MRI or positron emission tomography/CT scan

    * If the only measurable lesion is the plasmacytoma, it must be ≥ 1.5 cm in 1 dimension
* Must have ≥ 10% plasma cells as measured on the bone marrow aspirate, bone marrow biopsy, or labeling index
* No amyloidosis

PATIENT CHARACTERISTICS:

* Performance status 0-2
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 8.0 g/dL
* Creatinine ≤ 2.0 mg/dL (elevation above normal range should not be felt to be related to myeloma)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use 2 methods of effective contraception 4 weeks before, during, and for 4 weeks after completion of study treatment
* No uncontrolled infection
* No other active malignancy
* No New York Heart Association class III or IV heart disease
* No pre-existing neuropathy ≥ grade 2
* No concurrent major dental work

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Prior corticosteroids (for nonmalignant disorders) allowed
* Prior therapy with experimental agents not shown to have significant activity in MM, such as clarithromycin, dehydroepiandrosterone, and anakinra allowed
* No prior thalidomide or corticosteroids for MM
* No more than 3 doses of IV zoledronate or pamidronate within the past 12 months
* At least 3 months since prior radiotherapy, including radiotherapy for solitary plasmacytoma
* No concurrent oral bisphosphonate therapy for osteoporosis

Answer: C