RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma

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.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Neoplasms; Multiple Myeloma; Efficacy; Safety
• Intervention / Treatment: Drug: RDD; Drug: VDD

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xin Wang, PhD, MD; Phone Number: +86-531-68778331; Email: xinw@sdu.edu.cn
• Study Contact Backup: Name: Xin Liu, PhD, MD; Phone Number: +86-15168889791; Email: 13518611662@163.com

Study Locations

• China
  • Shandong
    • Jin'an, Shandong, China, 250012
      • Recruiting
      • Department of Hematology, Provincial Hospital Affiliated to Shandong University
      • Contact: Xin Liu, MD,PHD; Phone Number: 86-531-68778331; Email: 13518611662@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RDD group; Lenalidomide: 25mg, po, d1-21， Pegylated Liposomal Doxorubicin: 30-40mg/m2，ivgtt, d1 Dexamethasone: 20-40mg, po, d1，d8，d15，d22	Drug: RDD; Lenalidomide: 25mg, po, d1-21， Pegylated Liposomal Doxorubicin: 30-40mg/m2，ivgtt, d1 Dexamethasone: 20-40mg, po, d1，d8，d15，d22; Other Names: RDD group
Active Comparator: 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	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; Other Names: VDD group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response (CR)	meeting the standard IMWG response criteria (CR and VGCR) of NCCN guidelines (Version2. 2019)	At 8 months
partial remission (PR)	meeting the standard IMWG response criteria (PR) of NCCN guidelines (Version2. 2019)	At 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progressive free survival	the length of time during and after the treatment of MM that a patient lives with the disease but it does not get worse	At 3 months, 5 months, 8 months, 12 months, 18 months, 24 months and 36 months
overall survival (OS)	the percentage of MM patient who are alive after 3 years.	At 3 months, 5 months, 8 months, 12 months, 18 months, 24 months and 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects	Incidence of Treatment-Emergent Adverse Events	At 3 months, 5 months and 8 months

Collaborators and Investigators

• Sponsor: Shandong Provincial Hospital
• Investigators: Principal Investigator: Xin Wang, PhD, MD, Shandong Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 28, 2019
• First Submitted That Met QC Criteria: April 5, 2019
• First Posted (Actual): April 9, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: lenalidomide; multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: ShandongPH03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No