Comparation of Chidamide Plus VRD (Bortezomib, Lenalidomide, Dexamethasone) With VRD Regimen for Primary High-Risk Multiple Myeloma Patients

Study Overview
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Brief Summary
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In the phase I trial, dose escalation of chidamide will be performed at 4 different dosages (15mg, 20mg, 25mg, 30mg) for optimal dosage, in the phase II trial, the safety and efficacy of chidamide+VRD will be compared with that of VRD regimen.

Detailed Description
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In the phase I trial, dose escalation of chidamide will be performed at 4 different dosages (15mg, 20mg, 25mg, 30mg) for optimal dosage, which will be determined by efficacy and safety profiles of the patients; afterward, the optimal dosage of chidamide will be combined with VRD regimen, patients will be randomly assigned to chidamide+VRD group or VRD group, and their efficacy and safety will be compared.

Official Title
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Comparation of Chidamide Plus VRD (Bortezomib, Lenalidomide, Dexamethasone) With VRD Regimen for Primary High-Risk Multiple Myeloma Patients, a Phase I/II, Multiple Center, Randomized Clinical Trial

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Chidamide+VRD
* Drug: VRD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Diagnosed as multiple myeloma, and has one of the above: high risk karyotype, such as 17p-，t（4；14），t（14；16），t（14；20）或1q gain,1p-, double hit myeloma, triple hit myeloma, etc; RISS-3; IgD/IgE MM; with measurable extra-medullary plasmacytoma; flowcytometry showed peripheral blood plasma cell ≥0.165%； 2.Secretory MM should have measurable markers, including: specific M protein value (≥5g/L)； and/or involved flc ≥100mg/L； and/or measurable extramedullary foci (diameter>1cm on CT); 3.Age≥18 years, male or female; 4.ECOG 0-2 points, with life expectance ≥3 months; GA score <2; 5.ALT/AST level <2.5 times of the maximum of normal range; total bilirubin<1.5 times of normal maximum； 6.Neutrophil count≥1.5×109/L, platelet count≥50×109/L; 7.eGFR≥40ml/min，except in the case of myeloma-related nephropathy; 8.Normal left ventricular ejaculation rate, NYHA stage 1, pulmonary function GOLD stage 1; 9.Willing to accept the possibility of potential adverse events and efficacy observation by the investigators; 10.Being able to understand and signing the written consent, which should be signed prior to any procedure of the trial. Exclusion Criteria: 1.With ≥2 degree of peripheral neuropath or with pain; 2.Having received any of the medicine of the experiment regimen within 30 days prior to enrollment, pain-relieving radiotherapy is allowed; 3.With severe pulmonary/cardiac disfunction (including history of QT interval elongation, ventricular tachycardia, ventricular fibrillation, myocardial infraction) or other severe organ malfunction; 4.Patients in pregnancy or lactation; 5.Allergic constitution or being allergic to any drug within the regimen of the trial; 6.With uncontrolled mental diseases; 7.With active infection; 8.With non-myeloma-associated acute renal dysfunction; 9.With active hepatitis; 10.HIV positive; 11.History of other malignant tumor within 5 years prior to enrollment; except for the case of in situ cervical cancer and non-malignant melanoma; 12.With other conditions that the investigators think unfit for the trial.

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
Interventional Model Description: In this trial, patients will be randomly assigned to chidamide+VRD group or VRD group, and then treated with the corresponding regimen, and their safety and efficacy will be evaluated.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chidamide plus VRD<br>Chidamide:30mg d0,d3,d7,d10/Velcade:1.3mg/m2 d1,d4,d8,d11/ Dexamethasone: 10mg BID d1,d2,d4,d5,d8,d9,d10,d11/Lenalidomide: 25mg d1-d14 | Drug: Chidamide+VRD<br>* Chidamide:30mg d0,d3,d7,d10/Velcade:1.3mg/m2 d1,d4,d8,d11/ Dexamethasone: 10mg BID d1,d2,d4,d5,d8,d9,d10,d11/Lenalidomide: 25mg d1-d14<br>|
| Active Comparator: VRD<br>Velcade:1.3mg/m2 d1,d4,d8,d11/ Dexamethasone: 10mg BID d1,d2,d4,d5,d8,d9,d10,d11/Lenalidomide: 25mg d1-d14 | Drug: VRD<br>* Velcade:1.3mg/m2 d1,d4,d8,d11/ Dexamethasone: 10mg BID d1,d2,d4,d5,d8,d9,d10,d11/Lenalidomide: 25mg d1-d14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate | complete remission rate after treated by the corresponding regimen | at the time point 1 month after the last cycle | 
| incidence and severity of adverse events | any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure | from the date of the start of treatment to 36 months after last patient's enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | from date of inclusion to date of progression, relapse, or death from any cause | from the day of treatment to the date of first documented progression，up to 36 months after the last patient's enrollment; | 
| overall survival | from the date of inclusion to date of death, irrespective of cause | from the day of treatment to the date of first documented progression，up to 36 months after the last patient's enrollment |