CyBorD vs. PAD in the Treatment of Newly Diagnosed Multiple Myeloma

A Phase 3 Trial Comparing Cyclophosphamide,Bortezomib,and Dexamethasone (CyBorD) and Bortezomib,Doxorubicin,and Dexamethasone (PAD) in the Treatment of Newly Diagnosed Multiple Myeloma

Bortezomib-based triple-drug combination has greatly improved the response rate of multiple myeloma patients. Bortezomib,doxorubicin,and dexamethasone (PAD) is commonly used in clinical practice.Recent studies have found that cyclophosphamide, bortezomib,and dexamethasone (CyBorD)seems better than PAD in efficacy. However, there is no randomized phase 3 trial comparing these two regimens in the treatment of newly diagnosed multiple myeloma patients.In this study, the investigators will compare the efficacy and safety of these two regimens using once-weekly subcutaneous injection of bortezomib.

Study Overview

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

Detailed Description

Bortezomib-based triple-drug combination has greatly improved the response rate of multiple myeloma patients. Bortezomib,doxorubicin,and dexamethasone (PAD) is commonly used in clinical practice. Recent studies have found that cyclophosphamide, bortezomib,and dexamethasone (CyBorD)seems better than PAD in efficacy. However, there is no randomized phase 3 trial comparing these two regimens in the treatment of newly diagnosed multiple myeloma patients. Moreover, studies have found that subcutaneous injection of bortezomib can decrease the incidence rate of peripheral neuropathy induced by bortezomib, however, most center use twice-weekly administration of bortezomib. According to our experience, once-weekly subcutaneous injection of bortezomib can further decrease the incidence rate of peripheral neuropathy without compromising the efficacy. Thus, in this phase 3 trial, the investigators will compare the efficacy and safety of these two regimens using once-weekly subcutaneous injection of bortezomib.

• Study Type: Interventional
• Enrollment (Anticipated): 236
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Zhongjun Xia, MD; Phone Number: 020-87342439; Email: xiazhj@sysucc.org.cn

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:

• Newly diagnosis of multiple myeloma
• Eastern Cooperative Oncology Group (ECOG) status 0-3,
• Estimated survival time > 3 months
• Acceptable liver function (bilirubin<2.5×ULN, Alanine transaminase (ALT) or Aspartate Aminotransferase (AST)<2.5×ULN)
• No history of other malignancies
• No previous treatments including chemotherapy, radiotherapy, targeted therapy or stem cell transplantation
• No other serious diseases which conflict with the treatment in the present trial
• No concurrent treatments that conflict with the treatments in the present trial
• Voluntary participation and signed the informed consent.

Exclusion Criteria:

• The patients had the conditions below: clinically significant ventricular tachycardia (VT), atrial fibrillation (AF), heart block, myocardial infarction (MI), congestive heart failure (CHF), symptomatic coronary artery heart disease requiring medication;
• The patients participated in other clinical trials within the 30 days before enrollment or who are participating in other clinical studies
• The patients with neuropathy
• The patients with mentally ill / unable to obtain informed consent
• The patients with drug addiction, alcohol abuse which affects the long-term evaluation of test results
• The patients in pregnancy, lactation and women of childbearing age who do not want to take contraceptive measures subjects
• The patients with a history of allergy to test drug
• The patients not suitable to participate in the investigator judged by researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CyBorD regimen; this arm will receive cyclophosphamide (500mg/d,once-weekly),bortezomib(1.3mg/㎡，once-weekly,subcutaneous injection), and dexamethasone (40mg/d,once-weekly)(CyBorD) as induction therapy.	Drug: Cyclophosphamide; 500mg/d,once-weekly,per oral.; Other Names: endoxan; Drug: Bortezomib; 1.3mg/㎡,once-weekly,subcutaneous injection; Other Names: velcade; Drug: Dexamethasone; 40mg/d,once-weekly,per oral
ACTIVE_COMPARATOR: PAD regimen; this arm will receive bortezomib(1.3mg/㎡，once-weekly,subcutaneous injection), dexamethasone (40mg/d,once-weekly), and doxorubicin (9mg/㎡，d1-4)(PAD) as induction therapy.	Drug: Bortezomib; 1.3mg/㎡,once-weekly,subcutaneous injection; Other Names: velcade; Drug: Dexamethasone; 40mg/d,once-weekly,per oral; Drug: Doxorubicin; 9mg/㎡,d1-4; Other Names: adriamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
At least very good partial response rate (according to the criteria IMWG) after four cycles of induction therapy	compare the Response assessment in both arms: the Very good partial response rate (according to the criteria IMWG) achieved with four courses of CyBorD with with that achieved with four courses of PAD	date from randomization to 1 month after completion of 4 cycles of induction therapy (up to 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response rate(according to the criteria IMWG) after four cycles of induction therapy	compare the Response assessment in both arms: the complete response rate (according to the criteria IMWG) achieved with four courses of CyBorD with with that achieved with four courses of PAD	date from randomization to 1 month after completion of 4 cycles of induction therapy (up to 6 months)
At least partial response rate (according to the criteria IMWG) after four cycles of induction therapy	compare the Response assessment in both arms: the at least partial response rate (CR+VGPR+PR) (according to the criteria IMWG) achieved with four courses of CyBorD with with that achieved with four courses of PAD	date from randomization to 1 month after completion of 4 cycles of induction therapy (up to 6 months)

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Zhongjun Xia, Doctor, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (ANTICIPATED): April 1, 2018
• Study Completion (ANTICIPATED): May 1, 2018

Study Registration Dates

• First Submitted: February 8, 2015
• First Submitted That Met QC Criteria: February 11, 2015
• First Posted (ESTIMATE): February 12, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): April 20, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: peripheral neuropathy; cyclophosphamide; bortezomib; multiple myeloma; doxorubicin
• 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; 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; Antibiotics, Antineoplastic; Dexamethasone; Cyclophosphamide; Bortezomib; Doxorubicin
• Other Study ID Numbers: SYSUCC-MM-308