Back to resultsCombination of G-CSF, Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Multiple Myeloma
Primary Purpose
Myeloma, Bortezomib, Cyclophosphamide
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
G-CSF
Bortezomib
Cyclophosphamide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Myeloma
Eligibility Criteria
Inclusion Criteria:
- Male or female, aged ≥18 years, ≤ 80 years.
- Newly diagnosed multiple myeloma according to International Myeloma Working Group.
- Relapsed or bortezomib resistant multiple myeloma (MM), who didn't received bortezomib during the last line of therapy for MM prior to this study.
- Progressive disease according to International Myeloma Working Group.
- Negative pregnancy test for female with reproductive ability.
- Signed written informed consent.
Exclusion Criteria:
- The patient has a history of other active malignancies within 3 years prior to study entry.
- The patient exhibits evidence of clinically significant uncontrolled conditions including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal).
- Female patient is pregnant or breast-feeding.
- Known infection with HIV, active Hepatitis B or Hepatitis C.
- The patient has a history of prior toxicity from bortezomib, cyclophosphamide or dexamethasone that resulted in permanent discontinuation of treatments.
- Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to study drug administration.
- Uncontrolled hypertension (defined as systolic blood pressure[BP] > 160 millimeters of mercury (mmHg) or diastolic BP > 100mmHg).
- 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.
- 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.
- Known or suspected of not being able to comply with the trial protocol.
Having been previously enrolled in this clinical trial.
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Sites / Locations
- The Second Affiliated Hospital of Soochow UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
G-CSF/Bortez/Cyc/Dex
Arm Description
G-CSF IC on days 0, 1, 7, 8, 14, 15, 21 and 22. Bortezomib IV on days 1, 8, 15 and 22. Cyclophosphamide CIV on days 1, 8, 15 and 22. Dexamethasone IV on days 1, 2, 8, 9, 15, 16, 22 and 23.
Outcomes
Primary Outcome Measures
Overall 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.
Secondary Outcome Measures
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.
Overall Survival (OS)
Survival time is defined as the time from registration to death due to any cause.
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.
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.
Full Information
NCT ID
NCT02027220
First Posted
December 21, 2013
Last Updated
January 2, 2014
Sponsor
Second Affiliated Hospital of Soochow University
1. Study Identification
Unique Protocol Identification Number
NCT02027220
Brief Title
Combination of G-CSF, Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Multiple Myeloma
Official Title
Phase Ⅱ Study of G-CSF, Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Unknown status
Study Start Date
December 2013 (undefined)
Primary Completion Date
December 2015 (Anticipated)
Study Completion Date
December 2015 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Second Affiliated Hospital of Soochow University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloma, Bortezomib, Cyclophosphamide, Dexamethasone, Granulocyte Colony-Stimulating Factor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
G-CSF/Bortez/Cyc/Dex
Arm Type
Experimental
Arm Description
G-CSF IC on days 0, 1, 7, 8, 14, 15, 21 and 22. Bortezomib IV on days 1, 8, 15 and 22. Cyclophosphamide CIV on days 1, 8, 15 and 22. Dexamethasone IV on days 1, 2, 8, 9, 15, 16, 22 and 23.
Intervention Type
Drug
Intervention Name(s)
G-CSF
Intervention Description
G-CSF Intracutaneous injection (IC) on days 0, 1, 7, 8, 14, 15, 21 and 22, every four weeks.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Bortezomib Intravenous injection (IV) on days 1, 8, 15 and 22, every four weeks.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide, Continuously Intravenous injection (CIV) on days 1, 8, 15 and 22, every four weeks.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone Intravenous injection (IV) on days 1, 2, 8, 9, 15, 16, 22 and 23, every four weeks.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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
Secondary Outcome Measure Information:
Title
Number of participants with treatment related adverse events.
Description
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
Title
Overall Survival (OS)
Description
Survival time is defined as the time from registration to death due to any cause.
Time Frame
2 years
Title
Progression Free Survival (PFS)
Description
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
Title
Duration of Response (DOR)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, aged ≥18 years, ≤ 80 years.
Newly diagnosed multiple myeloma according to International Myeloma Working Group.
Relapsed or bortezomib resistant multiple myeloma (MM), who didn't received bortezomib during the last line of therapy for MM prior to this study.
Progressive disease according to International Myeloma Working Group.
Negative pregnancy test for female with reproductive ability.
Signed written informed consent.
Exclusion Criteria:
The patient has a history of other active malignancies within 3 years prior to study entry.
The patient exhibits evidence of clinically significant uncontrolled conditions including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal).
Female patient is pregnant or breast-feeding.
Known infection with HIV, active Hepatitis B or Hepatitis C.
The patient has a history of prior toxicity from bortezomib, cyclophosphamide or dexamethasone that resulted in permanent discontinuation of treatments.
Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to study drug administration.
Uncontrolled hypertension (defined as systolic blood pressure[BP] > 160 millimeters of mercury (mmHg) or diastolic BP > 100mmHg).
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.
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.
Known or suspected of not being able to comply with the trial protocol.
Having been previously enrolled in this clinical trial.
-
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
jinxiang fu, Doctor
Phone
86-512-67784-66
Email
lbzwz0907@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jinxiang Fu, M.D., PhD
Organizational Affiliation
Second Affiliated Hospital of Soochow University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215004
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jinxiang fu, doctor
Phone
86-512-67784066
Email
lbzwz0907@hotmail.com
First Name & Middle Initial & Last Name & Degree
jinxiang fu, doctor
12. IPD Sharing Statement
Learn more about this trial
Combination of G-CSF, Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Multiple Myeloma
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