A comparison of Bortezomib, Pomalidomide with low-dose Dexamethasone and Bortezomib, Lenalidomide with low-dose dexamethasone for newly-diagnosed multiple myeloma patients- A randomized phase III study.

Phase 3

Not yet recruiting

Conditions: Multiple myeloma, Newly diagnosed cases of multiple myeloma ,

Registration Number: CTRI/2019/07/020397

Lead Sponsor: Dr Lalit Kumar

Brief Summary: Multiple myeloma is a neoplastic disease of plasma cells. The treatment of advanced myeloma has undergone a major change in the past decade. From the use of cytotoxic chemotherapy in the past, the current approach is to use novel agents such as immuno-modulatory drugs and/or proteasome inhibitors in combination with steroids as the initial induction therapy. Triplet therapy combining a proteasome inhibitor and an immunomodulatory drug with steroid has provided the benefit of longer durations of remission compared to the older 2 drug combinations. Most patients will eventually relapse and need salvage therapy. Patients with a more durable response to the initial induction therapy tend to have improved life span. Hence the role of using more potent drugs in the newly diagnosed patients will ultimately translate into superior outcomes.

Newer thalidomide analogues such as lenalidomide and the recently approved pomalidomide are more potent immunomodulatory drugs and have multiple mechanisms of action notably inhibition of tumor angiogenesis, immunomodulation, stimulation of T cell activity, induction of apoptosis and inhibition of malignant plasma cell proliferation.

Large randomized phase III trials have compared bortezomib, lenalidomide and dexamethasone (VRd) with lenalidomide and dexamethasone (Rd) as induction therapy in newly-diagnosed MM patients (Durie B. , 2017). Median progression-free survival (PFS) was 43 versus 30 months (p<0.0037) and overall respectively. Similarly pomalidomide has also been tried with bortezomib and dexamethasone as phase 1/ 2 trials in patients with relapsed refractory MM. (Paludo, 2017), (Richardson P. , 2017).

Almost one third of patients have ISS III andhave poor outcome. Since, bortezomib and lenalidomide based combinationhave been shown to improve outcome for such patients (ISS III, poor riskcytogenetics) in phase II studies, we feelthat combining lenalidomide or pomalidomide and dexamethasone along withbortezomib may improve the outcome.

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: All

Target Recruitment: 252

Inclusion Criteria

a) Newly diagnosed cases of multiple myeloma with no prior chemotherapy (prior treatment with dexamethasone up to 2 weeks is acceptable).
Prior localized or palliative radiotherapy is acceptable.
b)Durie- Salmon stage II and III, ISS stage I,II,III c)Age between 18 and 70 years d)ECOG performance status of 0 to 2 e)Serum creatinine of â‰¤2.0 mg/dl f)Adequate liver function (serum bilirubin â‰¤1.5 mg/dl, AST and ALT < 2.5 times of upper limit of normal) g)Adequate hemogram absolute neutrophil count >1000/ cu.
and platelet count >75,000/ cu.mm.
and Hb>7g/dl h)Pre-existing peripheral neuropathy < grade 2 at the time of enrollment i)Pregnancy test negative for female patients of reproductive age j)Willing to participate (provide written informed consent).

Exclusion Criteria

a) Prior treatment with Bortezomib, Lenalidomide or Thalidomide b)Non-secretory multiple myeloma, monoclonal gammopathy of unknown significance (MGUS), or smoldering myeloma.
c)Uncontrolled diabetes mellitus d)Uncontrolled hypertension, unstable angina, inadequate cardiac function (abnormal ECG: rhythm disturbances), acute myocardial infarction within the last 6 months e)Severe psychiatric disorder that would make participation in the study difficult f)History of hypersensitivity reaction to mannitol, boron or bortezomib g)Patient is pregnant or lactating h)Active acute infection requiring systemic antibiotics, antifungals or antivirals within 2 weeks prior to start of study drug.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To estimate the progression-free survival in the two groups PVd and VRd	At end of 16 weeks of therapy

Secondary Outcome Measures

Name	Time	Method
To estimate the response rates CR VGPR and PR in the two groups	To assess the difference in the toxicity profile in the two groups

Trial Locations

Locations (1): Board Room
🇮🇳
South, DELHI, India
Board Room
🇮🇳South, DELHI, India
Dr Lalit Kumar
Principal investigator
011-26593405
lalitaiims@yahoo.com