Combination of G-CSF, Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Multiple Myeloma

NCT ID: NCT02027220

Last Updated: 2014-01-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2015-12-31

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.

Conditions

Myeloma; Bortezomib; Cyclophosphamide; Dexamethasone; Granulocyte Colony-Stimulating Factor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

G-CSF/Bortez/Cyc/Dex

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.

Group Type: EXPERIMENTAL

G-CSF

Intervention Type: DRUG

G-CSF Intracutaneous injection (IC) on days 0, 1, 7, 8, 14, 15, 21 and 22, every four weeks.

Bortezomib

Intervention Type: DRUG

Bortezomib Intravenous injection (IV) on days 1, 8, 15 and 22, every four weeks.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide, Continuously Intravenous injection (CIV) on days 1, 8, 15 and 22, every four weeks.

Dexamethasone

Intervention Type: DRUG

Dexamethasone Intravenous injection (IV) on days 1, 2, 8, 9, 15, 16, 22 and 23, every four weeks.

Interventions

G-CSF

G-CSF Intracutaneous injection (IC) on days 0, 1, 7, 8, 14, 15, 21 and 22, every four weeks.

Intervention Type: DRUG

Bortezomib

Bortezomib Intravenous injection (IV) on days 1, 8, 15 and 22, every four weeks.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide, Continuously Intravenous injection (CIV) on days 1, 8, 15 and 22, every four weeks.

Intervention Type: DRUG

Dexamethasone

Dexamethasone Intravenous injection (IV) on days 1, 2, 8, 9, 15, 16, 22 and 23, every four weeks.

Intervention Type: DRUG

Other Intervention Names

Velcade

Eligibility Criteria

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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• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

jinxiang fu

M.D., Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jinxiang Fu, M.D., PhD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Soochow University

Locations

The Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

jinxiang fu, Doctor

Role: CONTACT

lbzwz0907@hotmail.com

86-512-67784-66

Facility Contacts

jinxiang fu, doctor

Role: primary

lbzwz0907@hotmail.com

86-512-67784066

Other Identifiers

GBCD-001

Identifier Type: -

Identifier Source: org_study_id