Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by PETHEMA Foundation
Sponsor:
Collaborators:
Celgene Corporation
Amgen
Information provided by (Responsible Party):
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT02415413
First received: March 29, 2015
Last updated: November 10, 2016
Last verified: November 2016
  Purpose

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 Intervention Phase
Smoldering Multiple Myeloma
Drug: carfilzomib
Drug: Lenalidomide
Drug: Dexamethasone
Drug: Melphalan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of Carfilzomib, Lenalidomide and Dexamethasone (KRd) Plus High-dose Therapy With Melphalan and Autologous Stem Cell Transplantation, Followed by Consolidation With KRd, and Maintenance With Lenalidomide and Dexamethasone in Patients Under 65 Years With High Risk Smoldering Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 90
Study Start Date: May 2015
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: carfilzomib Drug: Lenalidomide Drug: Dexamethasone Drug: Melphalan

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).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  • Age older than 18 and younger than 65 years and candidates to receive high-dose therapy and autologous stem cell transplantation.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02415413

Contacts
Contact: Jesus F San Miguel, Dr sanmiguel@unav.es
Contact: M Victoria Mateos, Dr mvmateos@usal.es

Locations
Spain
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain
Contact: Laura Rosiñol, Dr       LROSINOL@clinic.ub.es   
Hospital Universitari Germans Trias i Pujol Recruiting
Barcelona, Spain
Contact: Albert Oriol, Dr       aoriol@iconcologia.net   
Hospital Clínico San Carlos Recruiting
Madrid, Spain
Contact: Rafael Martinez, Dr       rafaelbenigno.martinez@salud.madrid.org   
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: Joaquin Martinez, Dr       jmarti01@med.ucm.es   
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain
Contact: Javier Lopez, Dr       jljimenez@salud.madrid.org   
Hospital Universitario Morales Meseguer Recruiting
Murcia, Spain
Contact: Felipe De Arriba, Dr       Farriba@um.es   
Hospital Universitario Central de Asturias Recruiting
Oviedo, Spain
Contact: Ana Pilar González, Dr       anapilargonzalez@gmail.com   
Clínica Universidad de Navarra Recruiting
Pamplona, Spain
Contact: Jesús Fernando San Miguel, Dr       sanmiguel@unav.es   
Hospital de Son Llàtzer Recruiting
Plama de Mallorca, Spain
Contact: Joan Bargay, Dr       jbargay@hsll.es   
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain
Contact: M Victoria Mateos, Dr       mvmateos@usal.es   
Hospital General de Segovia Recruiting
Segovia, Spain
Contact: Jose M Hernandez, Dr       jhernandezma@saludcastillayleon.es   
Hospital Universitario Reina Sofía Recruiting
Sevilla, Spain
Contact: Miguel Ángel Álvarez, Dr       mangel.alvarez.sspa@juntadeandalucia.es   
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain
Contact: Jose A Perez, Dr       josea.perez.simon.sspa@juntadeandalucia.es   
Hospital Universitario de Canarias Recruiting
Tenerife, Spain
Contact: Miguel Teodoro Hernández, Dr       mthernan@ull.es   
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain
Contact: Ana Isabel Teruel, Dr       ateruelc@hotmail.com   
Hospital Universitario Doctor Peset Recruiting
Valencia, Spain
Contact: Javier de la Rubia, Dr       delarubia_jav@gva.es   
Hospital Clínico Universitario Lozano Blesa Recruiting
Zaragoza, Spain
Contact: Luis Palomera, Dr       lpalomera@salud.aragon.es   
Sponsors and Collaborators
PETHEMA Foundation
Celgene Corporation
Amgen
  More Information

Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT02415413     History of Changes
Other Study ID Numbers: GEM-CESAR
Study First Received: March 29, 2015
Last Updated: November 10, 2016

Keywords provided by PETHEMA Foundation:
Smoldering multiple myeloma
Carfilzomib
Lenalidomide
Melphalan
Dexamethasone
Autologous stem cell transplantation

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
Melphalan
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on May 25, 2017