E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the time to PBD from year 2 to year 4 in patients treated with monthly zoledronic acid in two consecutive years compared to patients treated with monthly zoledronic acid in four consecutive years. |
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E.2.2 | Secondary objectives of the trial |
compare low dose CT to conventional radiograhpy.
investigate serum bone markers in multiple myeloma |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Symptomatic Multiple Myeloma according to the IMWG criteria, regardless of bone disease status
-Signed Informed Consent
-Age ≥ 18 years
-Remaining life expectancy ≥ 2 years
-Any concurrently anti-myeloma treatment are allowed
Amendment: Patients may be included when they have received two years of zoledronic acid treatment outside clinical trials. They will proceed directly to randomisation
Inclusion criteria (amendment)
- Earlier diagnosed with symptomatic Multiple Myeloma according to the IMWG criteria, regardless of bone disease status
-Signed Informed Consent
-Age ≥ 18 years
-Remaining life expectancy ≥ 1 years
-Received 23-25 monthly infusions with zoledronic acid
-Any concurrent anti-myeloma treatment are allowed
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E.4 | Principal exclusion criteria |
-Previous treatment with bisphosphonate within the last 6 months
-Severely reduced renal function (creatinine clearance <30 mL/min despite fluid replacement)
-Known concurrent malignancy, excluding skin cancer
-Known hypersensitivity to zoledronic acid
-Pregnant or lactating women
-Women of childbearing potential or men engaging in sexual activity with a woman of childbearing potential who refuse to use contraception (safe methods of contraception are considered to be: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system ( IUS) bilateral tubal occlusion, vasectomy, and sexual abstinence. Contraception must be used until 56 days after the last infusion).
- Progressive bone disease diagnosed using bone imaging, less than or equal to three month prior to the randomization
- Developed BON during earlier zoledronic acid treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the time to PBD from year 2 to year 4 in patients treated with monthly zoledronic acid in two consecutive years compared to patients treated with monthly zoledronic acid in four consecutive years. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 358 patients with follow-up of at least 4 years |
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E.5.2 | Secondary end point(s) |
To compare the incidence of PBD from year 2 to year 4 in patients treated with monthly zoledronic acid in two consecutive years compared to patients treated with monthly zoledronic acid in four consecutive years.
To compare the incidence of sPBD from year 2 to year 4 in patients treated with monthly zoledronic acid in two consecutive years compared to patients treated with monthly zoledronic acid in four consecutive years.
To compare the incidence of bone healing from year 2 to year 4 in patients treated with monthly zoledronic acid in two consecutive years compared to patients treated with monthly zoledronic acid in four consecutive years.
To compare the overall survival from year 2 to year 4 in patients treated with monthly zoledronic acid in two consecutive years compared to patients treated with monthly zoledronic acid in four consecutive years.
To compare the incidence of BON from year 2 to year 4 in patients treated with monthly zoledronic acid in two consecutive years compared to patients treated with monthly zoledronic acid in four consecutive years.
To compare the development in QoL from year 2 to year 4 in patients treated with monthly zoledronic acid in two consecutive years compared to patients treated with monthly zoledronic acid in four consecutive years.
To compare the development in the bone markers CTX-I, PINP, bALP, and TRAP5b from year 2 to year 4 in the patients groups randomised to receive two or four years of treatment with zoledronic acid
To investigate in monthly measurements of the bone markers CTX-I, PINP, bALP, TRAP5b, or the ratios of these can be used to predict the development of PBD from year 2 to year 4.
To investigate the consistency between the diagnose “no bone disease” when using conventional radiography compared to low-dose CT at diagnosis*.
To investigate if the patients with inconsistency in bone disease status using the different imaging modalities at diagnosis are more likely to progress in bone disease compared to patients diagnosed with “no bone disease” using both modalities*.
To investigate if the three patients groups 1. consistent “no bone disease” 2. inconsistent bone disease 3. consistent “bone disease”, at diagnosis can be identified using the levels of the bone markers CTX-I, PINP, bALP, TRAP5b, ICTP, or the ratio of these.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 358 patients with follow-up of at least 4 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life
Bone markers
CT vs convertional radiographi |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |