Clinical trial NCT01852799
Conditions: Multiple Myeloma
Keywords: Multiple myeloma PAD ASCT Bone metabolites Bone marker
Sponsor: Shanghai Changzheng Hospital
Start date: 2012-12-01; Completion date: 2017-01-01
Enrollment: 18 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a multicentre; single arm study in subjects with newly diagnosed multiple myeloma.

The primary objectives of this study is to assess the effect of bortezomib combination therapy (PAD regimen) followed by ASCT on bone metabolites in patients with newly diagnosed multiple myeloma, as measured by ELISA methodology as previously described analyzing the change in biochemical bone marker compared with the baseline value: bone formation marker- bone alkaline phosphatase(bALP) and osteoblast inhibitor- Dickkopf-1(DKK-1）.

The secondary objectives of this study are:

1. Subgroup analysis for the change from baseline in biochemical bone marker based on whether or not Bisphosphonate was used.
2. Assessment of other bone markers parameters: bone formation marker -carboxy terminal propeptide of type I procollagen (PICP); bone resorption markers -carboxy terminal telopeptide region of type I collagen ( ICTP); osteoclast stimulators -osteoprotegerin(OPG), soluble receptor activator of nuclear factor kappaB ligand(sRANKL);
3. To observe the effect of bortezomib on bone mineral density (BMD) as measured by repeated quantitative CT-scan;
4. The evaluation of Skeletal related events (SRE) and appearance of new bone lesions;
5. To determine progression free survival (PFS), 1 year survival, overall survival and safety profile following treatment with PAD and ASCT as first-line therapy.

Detailed description:
After providing written informed consent, subjects will be evaluated for eligibility during a 14-day screening period. Eligible subjects will receive 4 cycles PAD treatment prior to ASCT. Bisphosphonate therapy can be administered as medically indicated and according to local practice.

After the end of the treatment phase, there will be 18 months follow-up period for every patient with visits at 4, 6, 12 and 18 months after the end of the treatment phase. In case the disease progresses before completing the 18 months of follow-up and once the subject started alternative MM treatment, study assessments will stop, except for survival follow-up which will be collected every 6 months by either a telephone call or a visit to the study site. The follow-up for survival will continue for all subjects until the last subject has completed follow-up. One interim analysis of efficacy and safety will be performed when all subjects have achieved the end of treatment. Safety will be assessed by the monitoring of adverse events, physical examination, vital signs measurements and clinical laboratory tests.

Arms: arm 1: Drug: Bortezomib, Adriamycin (Doxorubicin) /Epidoxorubicin(EPI), Dexamethasone.

After received induction therapy, patients will proceed to receive ASCT based on the willing of the patients and the decision of the investigators.
Interventions: intervention 1: PAD Followed by ASCT
Intervention descriptions: intervention 1: Drug: Bortezomib, Bortezomib (1.3mg/m2, iv, on day 1, 4, 8, 11, of each 28 day cycle)

Drug: Adriamycin (Doxorubicin) /EPI, Adriamycin (Doxorubicin) (9 mg/m2, iv, on days 1-4 of each 28 day cycle) or EPI (15mg/m2, iv, on days 1-4 of each 28 day cycle)

Drug: Dexamethasone, Dexamethasone (20mg, iv, on days 1-4, 8-11of each 28 day cycle)

After received induction therapy, patients will proceed to receive ASCT based on the willing of the patients and the decision of the investigators.

Protocol documents: