Clinical trial NCT03908138: RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
Official title: RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hematologic Neoplasms
Multiple Myeloma
Efficacy
Safety
Keywords: multiple myeloma
lenalidomide
Lead sponsor: Shandong Provincial Hospital
Sponsor class: OTHER_GOV
First posted: 2019-04-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The patients will be randomized either receiving RDD or receiving VDD therapy.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: complete response (CR)
timeFrame: At 8 months
measure: partial remission (PR)
timeFrame: At 8 months
Secondary outcomes:
measure: Progressive free survival
timeFrame: At 3 months, 5 months, 8 months, 12 months, 18 months, 24 months and 36 months
measure: overall survival (OS)
timeFrame: At 3 months, 5 months, 8 months, 12 months, 18 months, 24 months and 36 months
Other outcomes:
measure: Side effects
timeFrame: At 3 months, 5 months and 8 months
Locations:
city: Jin'an
country: China
facility: Department of Hematology, Provincial Hospital Affiliated to Shandong University
state: Shandong
Study officials:
affiliation: Shandong Provincial Hospital
name: Xin Wang, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: