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

NCT02415413 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: GEM-CESAR
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 16

Brief 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. Subsequently patients will start maintenance treatment during 24 months. Therefore, the total duration of the treatment will be approximately 36 months.

Conditions

Smoldering Multiple Myeloma

Keywords

Smoldering multiple myeloma; Carfilzomib; Lenalidomide; Melphalan; Dexamethasone; Autologous stem cell transplantation

Outcome Measures

Primary Outcomes (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

  4 months

Secondary Outcomes (9)

• Efficacy - 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

  60 months

• Efficacy -Months to overall survival

  60 months

• Relapse or progression patterns 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.

  Up to 84 months (from june 2020)

Study Arms (1)

Carlizomib lenalidomide and low dose dexamethasone

EXPERIMENTAL

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: carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Melphalan

Interventions

carfilzomib DRUG

Carlizomib lenalidomide and low dose dexamethasone

Lenalidomide DRUG

Carlizomib lenalidomide and low dose dexamethasone

Dexamethasone DRUG

Carlizomib lenalidomide and low dose dexamethasone

Melphalan DRUG

Carlizomib lenalidomide and low dose dexamethasone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Known active infection by human acquired immunodeficiency virus, B or C hepatitis virus.
• 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Celgene Corporation: collaborator
• Amgen: collaborator

Study Sites (16)

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario Morales Meseguer

Murcia, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Clínica Universidad de Navarra

Pamplona, Spain

Location

Hospital de Son Llàtzer

Plama de Mallorca, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hospital Universitario Reina Sofía

Seville, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Hospital Universitario Doctor Peset

Valencia, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

Related Publications (1)

• 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.

  PMID: 39038268 DERIVED

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

carfilzomib; Lenalidomide; Dexamethasone; Melphalan

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2015
• First Posted: April 14, 2015
• Study Start: May 1, 2015
• Primary Completion: July 5, 2018
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 10, 2022

Record last verified: 2022-09

Locations

ES (16)