Modified Bortezomib-based Combination Therapy for Multiple Myeloma

An Open-Label Phase IV Study of the Efficacy of Bortezomib-based Combination Therapy the Treatment of Subjects With Multiple Myeloma

To investigate the efficacy of a modified bortezomib based combination therapy for patients with multiple myeloma.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Thalidomide; Drug: Bortezomib; Drug: Mitoxsnteone

Detailed Description

Multiple myeloma (MM) is a common hematological malignancy in Chinese elderly population. The application of novel drugs improved the clinical outcome and survival of MM patients,even though MM remains an incurable hematological malignancy. Bortezomib is a typical one among these novel agents, its application resulted in great success, but its adverse events and high expense restricted its widely usage. Investigators modified the dose and frequency of bortezomib administration in combination therapy: Patients in the modified group received regimen with bortezomib (1.6mg/㎡) as an intravenous bolus once weekly on day 1, 8 in a 3 weeks cycle, in combination with dexamethasone,with or without doxorubicin/ cyclophosphamide/mitoxsnteone/thalidomide，while patients in the control group received similar combination therapy except with conventional bortezomib (1.3mg/㎡) administration twice weekly on day 1,4, 8,11.

The aim of this study is to investigate whether the modified bortezomib-based therapy may attain a similar efficacy as the conventional ones.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200080
    • Shanghai General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of multiple myeloma based on standard diagnosis criteria:

  • plasmacytomas on tissue biopsy
  • bone marrow plasmacytosis
  • monoclonal immunoglobulin spike on serum electrophoresis
  • lytic bone lesions.
• Must have relapsed or relapsed/refractory disease
• 18 years of age or older
• All baseline studies must be performed within 21 days of enrollment.
• ECOG performance status of 0 to 2

Exclusion Criteria:

• Renal insufficiency (serum creatinine levels > 2mg/dL)
• Concomitant therapy medications that include corticosteroids
• Peripheral neuropathy of Grade 3 or greater or painful Grade 2
• Evidence of mucosal or internal bleeding and/or platelet refractory
• ANC < 1000 cells/mm3
• Hemoglobin < 8.0 g/dL
• AST (SGOT and ALT) > 2 x ULN
• Intolerance to bortezomib or CC-5013 in the past or significant allergy to either compound, boron or mannitol
• Known hypersensitivity to thalidomide or the development of erythema nodosum
• Active infection or serious co-morbid medical condition
• Pregnant or breast-feeding women
• Prior malignancy with the last three years except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, on in-situ prostate cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: modified BZ group; Patients with newly diagnosed or pre-treated MM(prior therapy not including bortezomib) received regimen with bortezomib (1.6mg/㎡) as an intravenous bolus once weekly on day 1, 8 in a 3 weeks cycle, in combination with dexamethasone,with or without doxorubicin/ cyclophosphamide/mitoxsnteone/thalidomide	Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Thalidomide; Drug: Bortezomib; Other Names: velcade; Drug: Mitoxsnteone
Active Comparator: conventional BZ group; Patients with newly diagnosed or pre-treated MM(prior therapy not including bortezomib) received bortezomib (1.3mg/㎡) administration twice weekly on day 1,4, 8,11 in a 3 weeks cycle, in combination with dexamethasone,with or without doxorubicin/ cyclophosphamide/mitoxsnteone/thalidomide	Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Thalidomide; Drug: Bortezomib; Other Names: velcade; Drug: Mitoxsnteone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease responses to treatment	Response evaluated by changes of serum M-component(g/L) through Serum quantitative immunoglobulins and Serum immunofixation electrophoresis. (g/L)	one year

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Study Chair: Guohua Liu, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 23, 2015
• First Posted (Estimate): September 24, 2015

Study Record Updates

• Last Update Posted (Actual): May 4, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Antibiotics, Antineoplastic; Dexamethasone; Cyclophosphamide; Thalidomide; Bortezomib; Doxorubicin
• Other Study ID Numbers: 2010K059