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Smoldering Multiple MyelomaPhase 2NCT02415413

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

A Phase 2 study testing carfilzomib, Lenalidomide and Dexamethasone in people with Smoldering Multiple Myeloma, run by PETHEMA Foundation at 16 sites in Spain.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Smoldering Multiple Myeloma
What is being tested?
carfilzomib, Lenalidomide and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
16 sitesSpain
Study dates
May 2015to Jun 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Spain16 sites

  • Hospital Clínic de Barcelona

    Barcelona

  • Hospital Universitari Germans Trias i Pujol

    Barcelona

  • Hospital Clínico San Carlos

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario Ramón y Cajal

    Madrid

  • Hospital Universitario Morales Meseguer

    Murcia

  • Hospital Universitario Central de Asturias

    Oviedo

  • Clínica Universidad de Navarra

    Pamplona

  • Hospital de Son Llàtzer

    Plama de Mallorca

  • Hospital Universitario de Salamanca

    Salamanca

  • Hospital Universitario de Canarias

    Santa Cruz de Tenerife

  • Hospital Universitario Reina Sofía

    Seville

  • Hospital Universitario Virgen del Rocío

    Seville

  • Hospital Clínico Universitario de Valencia

    Valencia

  • Hospital Universitario Doctor Peset

    Valencia

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza

Other trials in Spain

About this study

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

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.

Read the 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).

Keywords
Smoldering multiple myeloma, Carfilzomib, Lenalidomide, Melphalan, Dexamethasone, Autologous stem cell transplantation
Medical subject headings
Smoldering Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02415413
Study groupRoleWhat they receive
Carlizomib lenalidomide and low dose dexamethasoneExperimentalInduction 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
Receives: Drug: carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Melphalan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy- Number of Immunophenotypic complete remission rate (Flow-CR) at day +100 after induction and HDT-ASCT

    Number of Immunophenotypic complete remission rate (Flow-CR) at day +100 after induction and HDT-ASCT

    Measured: 4 months

Secondary outcomes (9)

  1. Efficacy - Number of Response rates after the different parts of the treatment, induction, HDT-ASCT, consolidation and maintenance

    Number of Response rates after the different parts of the treatment, induction, HDT-ASCT, consolidation and maintenance

    Measured: up to 24 weeks

  2. Efficacy- Months to progression free survival

    Months to progression free survival

    Measured: 60 months

  3. Efficacy -Months to overall survival

    Months to overall survival

    Measured: 60 months

  4. Relapse or progression patterns in the group of patients requiring a rescue therapy after 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.

    Measured: Up to 84 months (from june 2020)

  5. Response rate of rescue therapy in the group of patients requiring a rescue therapy after 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.

    Measured: Up to 84 months (from june 2020)

  6. Progression Free Survival (PFS) and Overall Survival (OS) from the date of relapse / progression of disease

    PFS and OS from the date of relapse / progression of disease, in the group of patients requiring a rescue therapy.

    Measured: Up to 84 months (from june 2020)

  7. Biological studies in the group of patients requiring a rescue therapy.

    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.

    Measured: Up to 84 months (from june 2020)

  8. Study of patient immune profile in the group of patients requiring a rescue therapy.

    Assessment of patient immune profile at the moment of inclusion in this modification, and assessment of evolution under DPd treatment.

    Measured: Up to 84 months (from june 2020)

  9. Study of patient immune profile depending on type of relapse, in the group of patients requiring a rescue therapy.

    Assessment of immune profile at the moment of inclusion in patients in biochemical relapse vs. those in symptomatic relapse.

    Measured: Up to 84 months (from june 2020)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2015 (estimated)
  2. Study startMay 2015
  3. Primary completion5 Jul 2018
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02415413
Sponsor's protocol ID
GEM-CESAR
Status last verified
Sep 2022
First submitted
29 Mar 2015
Last updated
10 Sep 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Mateos MV, Martinez-Lopez J, Rodriguez Otero P, Gonzalez-Calle V, Gonzalez MS, Oriol A, Gutierrez NC, Rios-Tamayo R, Rosinol L, Alvarez Rivas MA, Bargay J, Gonzalez-Rodriguez AP, Alegre A, Escalante F, Inigo Rodriguez MB, De La Rubia J, Teruel AI, de Arriba F, Palomera L, Hernandez MT, Lopez Jimenez J, Reinoso-Segura M, Garcia Mateo A, Ocio EM, Paiva B, Puig N, Cedena MT, Blade J, Lahuerta JJ, San-Miguel JF; Spanish Myeloma Group (GEM-Pethema). Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance. J Clin Oncol. 2024 Sep 20;42(27):3247-3256. doi: 10.1200/JCO.23.02771. Epub 2024 Jul 22.

    PubMed 39038268

  • Puig N, Agullo C, Contreras T, Perez JJ, Aires I, Calasanz MJ, Garcia-Sanz R, Castro S, Martinez-Lopez J, Rodriguez-Otero P, Gonzalez-Calle V, Gonzalez MS, Oriol A, Gutierrez NC, Rios-Tamayo R, Rosinol L, Alvarez MA, Bargay J, Gonzalez-Rodriguez AP, Alegre A, Escalante F, Inigo MB, De la Rubia J, Teruel AI, De Arriba F, Palomera L, Hernandez MT, Lopez-Jimenez J, Reinoso M, Garcia-Mateo A, Ocio EM, Blade J, Lahuerta JJ, Cedena MT, Paiva B, Miguel JFS, Mateos MV. Single-point and kinetics of peripheral residual disease by mass spectrometry to predict outcome in patients with high-risk smoldering multiple myeloma included in the GEM-CESAR trial. Haematologica. 2024 Dec 1;109(12):4056-4066. doi: 10.3324/haematol.2024.285742.

    PubMed 38988266

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing carfilzomib, Lenalidomide and Dexamethasone in people with Smoldering Multiple Myeloma, run by PETHEMA Foundation at 16 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 10 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy- Number of Immunophenotypic complete remission rate (Flow-CR) at day +100 after induction and HDT-ASCT (time frame: 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02415413, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2022.

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