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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Bortezomib
* Drug: Dexamethasone
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CyBorD regimen<br>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<br>* 500mg/d,once-weekly,per oral.<br>* Other names: endoxan;Drug: Bortezomib<br>* 1.3mg/㎡,once-weekly,subcutaneous injection<br>* Other names: velcade;Drug: Dexamethasone<br>* 40mg/d,once-weekly,per oral<br>|
| Active Comparator: PAD regimen<br>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<br>* 1.3mg/㎡,once-weekly,subcutaneous injection<br>* Other names: velcade;Drug: Dexamethasone<br>* 40mg/d,once-weekly,per oral<br>Drug: Doxorubicin<br>* 9mg/㎡,d1-4<br>* Other names: adriamycin;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple myeloma, cyclophosphamide, bortezomib, doxorubicin, peripheral neuropathy