| CTRI Number |
CTRI/2019/07/020397 [Registered on: 29/07/2019] Trial Registered Prospectively |
| Last Modified On: |
28/07/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
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. |
|
Scientific Title of Study
|
Bortezomib, Pomalidomide plus low-dose Dexamethasone versus Bortezomib, Lenalidomide plus low-dose dexamethasone for newly-diagnosed multiple myeloma: A randomized phase III study. |
| Trial Acronym |
PVd vs VRd |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Lalit Kumar |
| Designation |
Professor and Head |
| Affiliation |
AIIMS, New Delhi |
| Address |
Room 234 2nd floor Department of Medical Oncology DrBRAIRCH
All India Institute of Medical Sciences Ansari Nagar New Delhi
South
DELHI
110029
India |
| Phone |
011-26593405 |
| Fax |
011-26588863 |
| Email |
lalitaiims@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Lalit Kumar |
| Designation |
Professor and Head |
| Affiliation |
AIIMS, New Delhi |
| Address |
Room 234 2nd floor Department of Medical Oncology DrBRAIRCH
All India Institute of Medical Sciences Ansari Nagar New Delhi
DELHI
110029
India |
| Phone |
011-26593405 |
| Fax |
011-26588863 |
| Email |
lalitaiims@yahoo.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Lalit Kumar |
| Designation |
Professor and Head |
| Affiliation |
AIIMS, New Delhi |
| Address |
Room 234 2nd floor Department of Medical Oncology DrBRAIRCH
All India Institute of Medical Sciences Ansari Nagar New Delhi
DELHI
110029
India |
| Phone |
011-26593405 |
| Fax |
011-26588863 |
| Email |
lalitaiims@yahoo.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of Medical Sciences New Delhi |
|
|
Primary Sponsor
|
| Name |
Dr Lalit Kumar |
| Address |
Room 234 2nd floor DrBRAIRCH AIIMS Ansari Nagar New Delhi 110029 |
| Type of Sponsor |
Other [Dr Lalit Kumar] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Lalit Kumar |
Board Room |
Department of Medical Oncology All India Institute of Medical Sciences Ansari Nagar New Delhi
South
DELHI |
011-26593405
011-26588863
lalitaiims@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee AIIMS New Delhi |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C900||Multiple myeloma, Newly diagnosed cases of multiple myeloma , |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Arm A PVd |
Arm A: PVd (Bortezomib, Pomalidomide with low-dose dexamethasone)
Inj Bortezomib 1.3mg/m2 SC on days 1,8, 15, 22
Cap Pomalidomide 4 mg days 1 to 21
Tab Dexamethasone 40 mg on days 1, 8, 15, 22
Cycle to be repeated every 28 days |
| Comparator Agent |
Arm B VRd |
Inj Bortezomib 1.3mg/m2 SC on days 1,8, 15, 22
Cap Lenalidomide 15 mg days 1 to 14
Tab Dexamethasone 40 mg on days 1, 8, 15, 22
Cycle to be repeated every 28 days |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
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 ≤2.0 mg/dl
f) Adequate liver function (serum bilirubin ≤1.5 mg/dl, AST and ALT < 2.5 times of upper limit of normal)
g) Adequate hemogram absolute neutrophil count >1000/ cu. mm. 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) |
|
| ExclusionCriteria |
| Details |
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 |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To estimate the progression-free survival in the two groups PVd and VRd |
At end of 16 weeks of therapy |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
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
To estimate the overall survival in the two groups
To analyze the quality of life of patients using the EORTC C30 version 3 quality of life questionnaire |
At the end of 4 cycles of therapy |
|
|
Target Sample Size
|
Total Sample Size="252"
Sample Size from India="252"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
31/07/2019 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
None yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
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 and
have poor outcome. Since, bortezomib and lenalidomide based combination
have been shown to improve outcome for such patients (ISS III, poor risk
cytogenetics) in phase II studies, we feel
that combining lenalidomide or pomalidomide and dexamethasone along with
bortezomib may improve the outcome. |