RATIONALE: Bortezomib may stop the growth of myeloma cells by blocking proteasome activity. Cyclophosphamide and dexamethasone may work in different ways to stop the growth of myeloma cells by stopping them from dividing or by killing the cells. Granulocyte Clone Stimulating Factor (G-CSF) possesses the ability to mobilize the plasma cells to detach from myeloma niche, so as to promote drug sensitivity.

PURPOSE: This phase Ⅱ trial is to study how well combination of G-CSF, bortezomib, cyclophosphamide and dexamethasone works in treating patients with multiple myeloma.

Myeloma cells reside in specialised microenvironments, which is called myeloma niche. Myeloma niche provides important cell-cell interactions and signalling molecules that regulate localization and proliferation of myeloma cells. stromal cell-derived factor 1(SDF-1)/Chemokine (C-X-C Motif) Receptor 4 (CXCR4) plays an important role in this process. G-CSF is reported to induce stem cell mobilization by decreasing bone marrow SDF-1. Our in vitro study found that G-CSF enhanced bortezomib activity by inhibiting SDF-1/CXCR4. Myeloma patients treated with Bortezomib, Cyclophosphamide and Dexamethasone have achieved a relatively good response, with an ORR about 80% and complete remission about 40%. We hypothesized that G-CSF may mobilize myeloma cells from myeloma niches thus to enhance bortezomib activity.

Inclusion Criteria:

1. Male or female, aged ≥18 years, ≤ 80 years.
2. Newly diagnosed multiple myeloma according to International Myeloma Working Group.
3. Relapsed or bortezomib resistant multiple myeloma (MM), who didn't received bortezomib during the last line of therapy for MM prior to this study.
4. Progressive disease according to International Myeloma Working Group.
5. Negative pregnancy test for female with reproductive ability.
6. Signed written informed consent.

Exclusion Criteria:

1. The patient has a history of other active malignancies within 3 years prior to study entry.

2. The patient exhibits evidence of clinically significant uncontrolled conditions including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal).

3. Female patient is pregnant or breast-feeding.

4. Known infection with HIV, active Hepatitis B or Hepatitis C.

5. The patient has a history of prior toxicity from bortezomib, cyclophosphamide or dexamethasone that resulted in permanent discontinuation of treatments.

6. Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to study drug administration.

7. Uncontrolled hypertension (defined as systolic blood pressure[BP] > 160 millimeters of mercury (mmHg) or diastolic BP > 100mmHg).

8. Myocardial infarction or unstable angina within the past 6 months prior to study drug administration. Heart failure of New York Heart Association function Class Ⅲ or Ⅳ prior to study drug administration.

9. System illness or other severe concurrent disease or alcoholism, which, in the judgement of the investigator, would make inappropriate for entry into this study or interfere significantly with the proper assessment of safety and efficacy of investigational treatments.

10. Known or suspected of not being able to comply with the trial protocol.

11. Having been previously enrolled in this clinical trial.

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