Carfilzomib in Treatment Patients Under 65 Years With High Risk Smoldering Multiple Myeloma

September 9, 2022 updated by: PETHEMA Foundation

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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).

  1. - 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).
  2. - 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).
  3. - The consolidation treatment will consist of 2 cycles of KRd, with the same doses and scheduled of the induction treatment.
  4. - 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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain
        • Hospital Clinic de Barcelona
      • Barcelona, Spain
        • Hospital Universitari Germans Trias i Pujol
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain
        • Hospital Clinico San Carlos
      • Madrid, Spain
        • Hospital Universitario Ramon y Cajal
      • Murcia, Spain
        • Hospital Universitario Morales Meseguer
      • Oviedo, Spain
        • Hospital Universitario Central de Asturias
      • Pamplona, Spain
        • Clinica Universidad de Navarra
      • Plama De Mallorca, Spain
        • Hospital de Son Llàtzer
      • Salamanca, Spain
        • Hospital Universitario de Salamanca
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocio
      • Sevilla, Spain
        • Hospital Universitario Reina Sofia
      • Tenerife, Spain
        • Hospital Universitario de Canarias
      • Valencia, Spain
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain
        • Hospital Universitario Doctor Peset
      • Zaragoza, Spain
        • Hospital Clínico Universitario Lozano Blesa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • In the investigator's opinion, the patient must be able to fulfill all the clinical trial requirements.
  • The patient must voluntarily sign the informed consent before any study procedure that is not part of the standard of care for these patients is performed, with the patient's knowledge that he/she may withdraw from the study at any time, without prejudice to his/her future care.
  • The patient must be aged between 18 and 70 years, and eligible to receive high-dose therapy and autologous peripheral blood stem cell transplant.
  • The patient must be diagnosed with smoldering multiple myeloma at high risk of progressing to symptomatic multiple myeloma, or at ultra high risk of progression to symptomatic disease, defined by:
  • smoldering multiple myeloma at high risk of progression to symptomatic disease:

Bone marrow infiltration with plasma cells (PCs) greater than or equal 10% and presence of a monoclonal component, immunoglobulin G (IgG) greater than3 g/dL or IgA greater than 2 g/dL or Bence Jones proteinuria greater than 1 g/24h and absence of lytic lesions, hypercalcemia, renal failure (creatinine less than 2 mg/dL) and anemia (hemoglobin greater than 10 gr/dL or not 2 gr/dL below the lower limit of normal).

Bone marrow infiltration with PCs greater than or equal 10% OR IgG greater than 3 g/dL or immunoglobulin A (IgA) greater than 2 g/dL or Bence Jones proteinuria greater than 1g/24h (but not both together) and always in the absence of lytic lesions, hypercalcemia, renal failure and anemia. These patients may be included in the study if they meet the following additional criteria: A percentage of phenotypically aberrant plasma cells (PCs) within the bone marrow (BM) PC compartment (aPC/ BM PC) greater than or equal 95% and immunoapheresis, defined as a reduction in the levels of 1 or 2 immunoglobulin (Igs) of more than 25% compared with the normal values of the corresponding Ig.

- smoldering multiple myeloma at ultra high risk of progression to symptomatic disease:

Presence of more than 1 focal lesion in MRI (ideally whole body MRI).

Infiltration in the BM equal or higher than 60%.

Ratio of involved/uninvolved serum Friend leukemia cell (FLC) higher than 100.

  • The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status less than 2.
  • The patient must be able to attend the scheduled visits.
  • Women of childbearing potential must have a negative pregnancy test (serum or urine) within the 14 days before the starting the study drug. In addition, sexually active women must agree to use contraceptive methods (hormone contraceptives [oral, injectable or implanted], tubal ligation, intrauterine device, barrier contraceptives with spermicide or have a vasectomised partner) while receiving the study drug. Women of childbearing potential must agree to undergo pregnancy tests every 4 weeks while receiving the study drug (every 14 days for women with irregular menstrual cycles) and 4 weeks after the last dose of study drug.

Exclusion Criteria:

  • Any physical condition or psychiatric disorder that would prevent the patient from signing or understanding the informed consent form.
  • Previous treatment for smoldering multiple myeloma.
  • Pregnancy or breastfeeding.
  • Presence of lytic lesions, anemia, renal failure or hypercalcemia.
  • Any of the following laboratory abnormalities:

Absolute neutrophil count (ANC) less than 1,000/mm3

Platelet count less than 75,000/mm3.

Serum GOT or glutamic pyruvic transaminase (GPT) greater than 3 x upper limit of normal

Serum total bilirubin greater than 2 x upper limit of normal

  • Prior history of neoplasm other than multiple myeloma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the patient has been disease-free for > 5 years.
  • Major surgery within 4 weeks before inclusion in the study.
  • Known active infection by human acquired immunodeficiency virus, B or C hepatitis virus.
  • Any investigational drug within 30 days before inclusion in the study.
  • Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrolment.
  • Unstable angina or myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
  • Uncontrolled hypertension or uncontrolled diabetes.
  • Significant neuropathy (Grades 3?4, or Grade 2 with pain) within 14 days prior to enrollment.
  • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib).
  • Contraindication to any of the required concomitant drugs or supportive treatments, including intolerance to hydration due to pre-existing pulmonary or cardiac impairment.
  • Left ventricular ejection fraction (LVEF) less than 40
  • Pulmonary hypertension

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: Lenalidomide
Drug: Dexamethasone
Drug: Melphalan
Drug: carfilzomib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
4 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
up to 24 weeks
Efficacy- Months to progression free survival
Time Frame: 60 months
Months to progression free survival
60 months
Efficacy -Months to overall survival
Time Frame: 60 months
Months to overall survival
60 months
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.
Up to 84 months (from 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.
Up to 84 months (from june 2020)
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.
Up to 84 months (from june 2020)
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.
Up to 84 months (from june 2020)
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.
Up to 84 months (from june 2020)
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.
Up to 84 months (from june 2020)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PETHEMA Foundation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Celgene Corporation
Amgen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 5, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 29, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 10, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 9, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GEM-CESAR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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