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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
G-CSF Intracutaneous injection (IC) on days 0, 1, 7, 8, 14, 15, 21 and 22, every four weeks.
Bortezomib Intravenous injection (IV) on days 1, 8, 15 and 22, every four weeks.
Cyclophosphamide, Continuously Intravenous injection (CIV) on days 1, 8, 15 and 22, every four weeks.
Dexamethasone Intravenous injection (IV) on days 1, 2, 8, 9, 15, 16, 22 and 23, every four weeks.
The Second Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGOverall Response Rate (ORR)
Defined as the portion of patients whose best response is equal to or better than partial response (PR), including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to International Myeloma Working Group (IMWG). Response was confirmed after every cycle of treatment. Stringent complete response (sCR): Normal free light chain (FLC) ration, plus criteria for complete response. Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in the bone marrow. Very Good Partial Response(VGPR): Positive immunofixation but negative electrophoresis; ≥90% reduction in serum M-component; Urine M-component ≤ 100mg per 24 hours. Partial Response (PR): ≥50% reduction in serum M-component and/or Urine M-component ≥90% reduction or \< 200mg per 24 hours.
Time frame: 4 months
Number of participants with treatment related adverse events.
Adverse Events (AE) are assessed according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 3.0. The maximum grade for each type of AE will be recorded for each patient. Grade 1: Mild AE. Grade 2: Moderate AE. Grade 3: Severe AE. Grade 4: Life-threatening or disabling AE. Grade 5: Death related AE.
Time frame: participants will be followed for the duration of hospital stay, an expected average of 4 weeks
Overall Survival (OS)
Survival time is defined as the time from registration to death due to any cause.
Time frame: 2 years
Progression Free Survival (PFS)
PFS is defined as the time from registration to the earliest date of documented disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death.
Time frame: 2 years
Duration of Response (DOR)
Duration of response will be calculated from the date of first evidence of response until the date of progression in the subset of patients with confirmed hematologic responses.
Time frame: 2 years
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