RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma

NCT ID: NCT03908138

Last Updated: 2019-11-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-30
• Study Completion Date: 2022-12-31

Brief Summary

Multiple myeloma (MM) is a common malignant hematology disease. The development of proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) significantly improved the survival of MM patients. IMiDs have multiple effects in MM therapy. Except for direct cytotoxicity, IMiDs also play a variety of immune regulatory roles. Lenalidomide, a kind of IMiDs, was usually used in the therapy of relapsed/refractory MM. The efficacy and safety of RDD (lenalidomide, pegylated liposomal doxorubicin, dexamethasone) in newly diagnosed patients with MM still needs to be further validated.

Detailed Description

The therapy regimens of MM were very limited before 2000, mainly including VAD (vincristine, doxorubicin, dexamethasone), methylpheniram, corticosteroids and autologous stem cell transplantation (ASCT). The development of proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) in the 2000's significantly improved the survival of MM patients. Combined chemotherapy containing new drugs has become the first-line therapy for the treatment of newly diagnosed MM patients.

In addition to direct cytotoxicity, IMiDs also play a variety of immune regulatory roles. The effects on immune system include reducing TNF-α, IL-1β, IL-6 and IL-12, increasing production of IL-2 and IFN-γ, increasing T cell initiation, enhancing the absorption of tumor antigen by dendritic cells (DCs), enhancing the efficiency of antigen presentation, inhibiting regulatory T cells (Treg), and enhancing the activity of natural killer cells (NK) and NKT cells. Lenalidomide, a kind of IMiDs, also have the effects on osteoclasts, which are important in bone disease in MM patients.

In 2006, the combination of lenalidomide and dexamethasone (RD) was approved in the United States for the treatment of relapsed/refractory MM. The RD regimen was approved for the treatment of newly diagnosed MM patients in 2015. Four lenalidomide-containing triple drug regimens were approved for the treatment of relapsed/refractory MM from 2015 to 2016. However, the application of lenalidomide-containing triple drug regimens in newly diagnosed patients with multiple myeloma needs to be further validated. Therefore, we designed the randomized controlled clinical study and aimed to compare the efficacy and safety between RDD (lenalidomide, pegylated liposomal doxorubicin, dexamethasone) and VDD (bortezomib, pegylated liposomal doxorubicin, dexamethasone) in newly diagnosed patients with MM.

Conditions

Hematologic Neoplasms; Multiple Myeloma; Efficacy; Safety

Keywords

multiple myeloma; lenalidomide

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RDD group

Lenalidomide: 25mg, po, d1-21， Pegylated Liposomal Doxorubicin: 30-40mg/m2，ivgtt, d1 Dexamethasone: 20-40mg, po, d1，d8，d15，d22

Group Type: ACTIVE_COMPARATOR

RDD

Intervention Type: DRUG

Lenalidomide: 25mg, po, d1-21， Pegylated Liposomal Doxorubicin: 30-40mg/m2，ivgtt, d1 Dexamethasone: 20-40mg, po, d1，d8，d15，d22

VDD group

Bortezomib:1.3mg/m2，ih，d1，d4，d8，d11 Pegylated Liposomal Doxorubicin: 30-40mg/m2，ivgtt, d1 Dexamethasone: 20 mg, ivgtt, d1, 2, 4, 5, 8, 9, 11,12

Group Type: ACTIVE_COMPARATOR

VDD

Intervention Type: DRUG

Bortezomib:1.3mg/m2，ih，d1，d4，d8，d11 Pegylated Liposomal Doxorubicin: 30-40mg/m2，ivgtt, d1 Dexamethasone: 20 mg, ivgtt, d1, 2, 4, 5, 8, 9, 11,12

Interventions

RDD

Lenalidomide: 25mg, po, d1-21， Pegylated Liposomal Doxorubicin: 30-40mg/m2，ivgtt, d1 Dexamethasone: 20-40mg, po, d1，d8，d15，d22

Intervention Type: DRUG

VDD

Bortezomib:1.3mg/m2，ih，d1，d4，d8，d11 Pegylated Liposomal Doxorubicin: 30-40mg/m2，ivgtt, d1 Dexamethasone: 20 mg, ivgtt, d1, 2, 4, 5, 8, 9, 11,12

Intervention Type: DRUG

Other Intervention Names

RDD group; VDD group

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of symptomatic (active) MM;
• Ages ≥18 years old, ≤65 years old;
• ECOG score: 0-2;
• Liver function: transaminase≤2.5×upper limit of normal value，bilirubin≤1.5×upper limit of normal value;
• Renal function: serum creatinine is 44-176 mmol/L;
• LVEF≥50%;
• New York Heart Association (NYHA) heart function classification is I-II grade;
• Signed informed consent.

Exclusion Criteria

• Severe complications or severe infection;
• Severe heart disease history, including ventricular tachycardia (VT), atrial fibrillation (AF), heart block, myocardial infarction (MI), congestive heart failure (CHF), coronary heart disease patients needed therapy;
• Severe allergic constitution, or those who are allergic to or intolerant of drug composition in chemotherapy regimens; with other malignant tumors in the past 5 years;
• Patients participate in other clinical studies;
• Patients are not suitable for the study;
• Other contraindications for ASCT therapy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Wang Xin

Director of Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xin Wang, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Shandong Provincial Hospital

Locations

Department of Hematology, Provincial Hospital Affiliated to Shandong University

Jin'an, Shandong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xin Wang, PhD, MD

Role: CONTACT

Phone: +86-531-68778331

Email: xinw@sdu.edu.cn

Xin Liu, PhD, MD

Role: CONTACT

Phone: +86-15168889791

Email: 13518611662@163.com

Facility Contacts

Xin Wang, MD, PHD

Role: primary

Xin Liu, MD,PHD

Role: backup

Other Identifiers

ShandongPH03

Identifier Type: -

Identifier Source: org_study_id