Carfilzomib in Treatment Patients Under 65 Years With High Risk Smoldering Multiple Myeloma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02415413|
Recruitment Status : Active, not recruiting
First Posted : April 14, 2015
Last Update Posted : February 17, 2021
Patients included in the study will receive induction treatment during 6 months, followed by receive high-dose therapy followed by peripheral blood stem cell transplantation.
Approximately 3 months after peripheral blood stem cell transplantation patients will receive consolidation treatment during 2 months.
Subsequently patients will start maintenance treatment during 24 months. Therefore, the total duration of the treatment will be approximately 36 months.
|Condition or disease||Intervention/treatment||Phase|
|Smoldering Multiple Myeloma||Drug: carfilzomib Drug: Lenalidomide Drug: Dexamethasone Drug: Melphalan||Phase 2|
This clinical trial is a multicenter Phase II study designed to evaluate the efficacy and toxicity of an intensive therapeutic approach in 90 patients with asymptomatic high risk multiple myeloma (SMM).
- - Patients will receive an induction treatment consisting of 6 cycles of carfilzomib, lenalidomide and low-dose dexamethasone (KRd): patients will receive carfilzomib 20-36 mg/m2 IV on days 1, 2, 8, 9, 15 and 16; with oral lenalidomide 25 mg daily on days 1-21, subsequently there will be a rest period of a week (from day 22 to day 27). Moreover, oral dexamethasone 40mg daily will be administered weekly (days 1, 8, 15 and 22).
- - Following the induction treatment, patients will receive high-dose (200 mg/m2) melphalan-based treatment administered via the intravenous route followed by peripheral blood stem cell transplantation (HDT-ASCT).
- - The consolidation treatment will consist of 2 cycles of KRd, with the same doses and scheduled of the induction treatment.
- - Maintenance treatment: all patients, without progression to symptomatic multiple myeloma or toxicity requiring discontinuation of the trial, will receive maintenance treatment during 24 cycles.
This maintenance treatment comprises the administration of lenalidomide 10mg on days 1-21, followed by a rest period of 1 week, with the weekly administration of dexamethasone 20mg.
Treatment will be administrated until the end of the maintenance, although patients will continue in the trial.
If biological progression is observed following the discontinuation of the treatment, lenalidomide and dexamethasone will be reinstituted in order to control the disease again. Lenalidomide 10 mg will be administrated on days 1-21 combined with dexamethasone 20mg on days 1, 8, 15 and 22. All patients will be monitored for asymptomatic disease progression and to collect data regarding on overall survival (OS).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Multicenter Study of Carfilzomib, Lenalidomide and Dexamethasone (KRd) as Induction Therapy, Followed by High-dose Therapy With Melphalan and Autologous Peripheral Blood Stem Cell Transplantation, Consolidation With KRd, and Maintenance With Lenalidomide and Dexamethasone in Patients ≤ 70 Years Old With Smoldering Multiple Myeloma (SMM) With High Risk of Progression to Symptomatic Myeloma|
|Actual Study Start Date :||May 2015|
|Actual Primary Completion Date :||July 5, 2018|
|Estimated Study Completion Date :||June 2027|
Experimental: Carlizomib lenalidomide and low dose dexamethasone
Induction treatment: patients included in the trial will receive an induction treatment for approximately 6 months (6 cycles of carfilzomib, lenalidomide and low dose dexamethasone (KRd)). After the third cycle of KRd, all patients will be mobilized with colony stimulating factor (G-CSF) alone to collect peripheral blood stem cell for the ASCT.
High dose therapy followed by autologous stem cell transplantation: patients will receive melphalan 200 mg/m2 via intravenous followed by autologous stem cell transplantation (HDT-ASCT).
Consolidation treatment: approximately 3 months after the autologous stem cell transplantation, patients will receive consolidation treatment for 2 months (2 cycles of carfilzomib, lenalidomide and low dose dexamethasone (KRd)).
Maintenance treatment: subsequently they will start a maintenance treatment that will be administered for approximately 24 months (24 cycles of lenalidomide and low dose dexamethasone
- Efficacy- Number of Immunophenotypic complete remission rate (Flow-CR) at day +100 after induction and HDT-ASCT [ Time Frame: 4 months ]Number of Immunophenotypic complete remission rate (Flow-CR) at day +100 after induction and HDT-ASCT
- Efficacy - Number of Response rates after the different parts of the treatment, induction, HDT-ASCT, consolidation and maintenance [ Time Frame: up to 24 weeks ]Number of Response rates after the different parts of the treatment, induction, HDT-ASCT, consolidation and maintenance
- Efficacy- Months to progression free survival [ Time Frame: 60 months ]Months to progression free survival
- Efficacy -Months to overall survival [ Time Frame: 60 months ]Months to overall survival
- Relapse or progression patterns in the group of patients requiring a rescue therapy after june 2020. [ Time Frame: Up to 84 months (from june 2020) ]Relapse or progression patterns after first line treatment with KRd->PBPCT->KRd->Rd, in the group of patients requiring a rescue therapy after june 2020.
- Response rate of rescue therapy in the group of patients requiring a rescue therapy after june 2020. [ Time Frame: Up to 84 months (from june 2020) ]Response rate achieved with daratumumab, pomalidomide and dexamethasone (DPd) as rescue therapy, by evaluating all response categories, including immunophenotypic response, sCR, CR, VGPR, PR and SD.
- Progression Free Survival (PFS) and Overall Survival (OS) from the date of relapse / progression of disease [ Time Frame: Up to 84 months (from june 2020) ]PFS and OS from the date of relapse / progression of disease, in the group of patients requiring a rescue therapy.
- Biological studies in the group of patients requiring a rescue therapy. [ Time Frame: Up to 84 months (from june 2020) ]Phenotypic and molecular assessment of the tumor clone that appears in the moment of relapse or disease progression (DP), and comparison against the tumor clone characterized at the moment of inclusion in the first part of the trial.
- Study of patient immune profile in the group of patients requiring a rescue therapy. [ Time Frame: Up to 84 months (from june 2020) ]Assessment of patient immune profile at the moment of inclusion in this modification, and assessment of evolution under DPd treatment.
- Study of patient immune profile depending on type of relapse, in the group of patients requiring a rescue therapy. [ Time Frame: Up to 84 months (from june 2020) ]Assessment of immune profile at the moment of inclusion in patients in biochemical relapse vs. those in symptomatic relapse.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02415413
|Hospital Clínic de Barcelona|
|Hospital Universitari Germans Trias i Pujol|
|Hospital Clínico San Carlos|
|Hospital Universitario 12 de Octubre|
|Hospital Universitario Ramón y Cajal|
|Hospital Universitario Morales Meseguer|
|Hospital Universitario Central de Asturias|
|Clínica Universidad de Navarra|
|Hospital de Son Llàtzer|
|Plama De Mallorca, Spain|
|Hospital Universitario de Salamanca|
|Hospital Universitario Reina Sofía|
|Hospital Universitario Virgen del Rocío|
|Hospital Universitario de Canarias|
|Hospital Clínico Universitario de Valencia|
|Hospital Universitario Doctor Peset|
|Hospital Clínico Universitario Lozano Blesa|