A study of carfilzomib, lenalidomide and dexamethasone (KRd) plus high-dose therapy with melphalan-200 and autologous stem cell transplantation, followed by consolidation with KRd, and maintenance with lenalidomide and dexamethasone in patients with high risk smoldering multiple myeloma (SMM) under 65 years
- Conditions
- Smoldering multiple myelomaMedDRA version: 17.1Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2014-002948-40-ES
- Lead Sponsor
- Fundación PETHEMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
1.-In the investigator's opinion, the patient must be able to fulfill all the clinical trial requirements.
2.-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.
3.-Age older than 18 and younger than 65 years and candidates to receive high-dose therapy and autologous stem cell transplantation.
4.-The patient must be diagnosed with smoldering MM at high risk of progressing to symptomatic MM, or at ultra high risk of progression to symptomatic disease, defined by:
- SMM at high risk of progression to symptomatic disease:
a. Bone marrow infiltration with plasma cells (PCs) greater than or equal 10% and presence of a monoclonal component, 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).
b. Bone marrow infiltration with PCs greater than or equal 10% OR IgG greater than 3 g/dL or 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 immunoparesis, 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.
- SMM at ultra high risk of progression to symptomatic disease:
a. Presence of more than 1 focal lesion in MRI (ideally whole body MRI).
b. Infiltration in the BM equal or higher than 60%.
c. Ratio of involved/uninvolved serum FLC higher than 100.
5.-The patient must have an ECOG performance status less than 2.
6.-The patient must be able to attend the scheduled visits.
7.-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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.-Any physical condition or psychiatric disorder that would prevent the patient from signing or understanding the informed consent form.
2.-Previous treatment for smoldering multiple myeloma.
3.-Pregnancy or breastfeeding.
4.-Presence of lytic lesions, anemia, renal failure or hypercalcemia.
5.-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 GPT greater than 3 x upper limit of normal
-Serum total bilirubin greater than 2 x upper limit of normal
6.-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.
7.-Major surgery within 4 weeks before inclusion in the study.
8.-Known active infection by human aquired immunodeficiency virus, B or C hepatitis virus.
9.-Any investigational drug within 30 days before inclusion in the study.
10.-Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrolment.
11.-Unstable angina or myocardial infarction within 6 months prior to enrollment, 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.
12.-Uncontrolled hypertension or uncontrolled diabetes.
13.-Significant neuropathy (Grades 3?4, or Grade 2 with pain) within 14 days prior to enrollment.
14.-Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib).
15.-Contraindication to any of the required concomitant drugs or supportive treatments, including intolerance to hydration due to pre-existing pulmonary or cardiac impairment.
16.-LVEF less than 40
17.-Pulmonary hypertension
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method