Pomalidomide combined with Carfilzomib and Dexamethasone (PCd) for induction and consolidation followed by Pomalidomide combined with Dexamethason vs Pomalidomide maintenance for patients with Multiple Myeloma in first relapse after prior 1st line treatment with Lenalidomide and Bortezomib.
- Conditions
- Multiple Myeloma10018865
- Registration Number
- NL-OMON53109
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 52
- Included in EMN02/HO95 trial. Induction therapy followed by autologous stem
cell transplant (AutoSCT) and consolidation/ maintenance will be considered as
one regimen.
- The subject must understand and voluntarily sign an informed consent document
prior to any study related assessments/procedures.
- Age >= 18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Documented diagnosis of multiple myeloma and measurable disease (serum
M-protein >= 10 g/L or urine M-protein >= 200 mg/24 hours or abnormal FLC ratio
with involved free light chain (FLC) > 100 mg/L) or proven plasmacytoma by
biopsy).
- Documented progression or refractory multiple myeloma as per the IMWG
uniform response criteria (Durie, 2006) during or after the EMN02/HO95 trial.
- Normal renal function with a Creatinine Clearance > 45mL/min according to the
Modification of Diet in Renal Disease (MDRD) equation for estimation of
Glomerular Filtration Rate (GFR)
- WHO performance status score of 0, 1 or 2.
- Patients must be willing and capable to use adequate contraception during the
therapy (all men, all pre-menopausal women).
- Patients must be able to adhere to the requirements of the Pregnancy
Prevention Risk Management Plan.
- Patients must be eligible for autologous stem cell transplantation when not
previously given in first line treatment.
- All subjects must agree to refrain from donating blood while on study drug
and for 28 days after discontinuation from this study treatment.
-All subjects must agree not to share medication.
-Patient received more than 1 regimen (EMN02/HO95), except local radiotherapy.
-Absolute neutrophil count (ANC) <1.0 x 109/L, unless related to MM.
-Platelet count < 75 x 109/L, unless related to MM.
-Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L).
-Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human
erythropoietin use is permitted).
-Significant hepatic dysfunction (Serum SGOT/AST or SGPT/ALT > 3.0 x upper
limit of normal (ULN) or serum total bilirubin > 3.0 x ULN)
-Prior history of malignancies, other than MM, unless the subject has been free
of the disease for >= 5 years. Exceptions include the following:
Basal or squamous cell carcinoma of the skin.
* Carcinoma in situ of the cervix or breast.
Incidental histological finding of prostate cancer (TNM stage of T1a or
T1b).
- Previous therapy with pomalidomide or carfilzomib.
- Hypersensitivity to thalidomide, lenalidomide, bortezomib or dexamethasone .
- Peripheral neuropathy >= Grade 2.
- Subjects who received an allogeneic bone marrow or allogeneic peripheral
blood stem cell transplant less than 12 months prior to initiation of study
treatment
- LVEF <= 40%.
- QTc > 450 msec.
- History of torsade de pointes.
- History of ventricular tachycardia, ventricular fibrillation.
- Uncontrolled atrial fibrillation/flatter.
- Congestive heart failure (NY Heart Association Class III or IV).
- Myocardial infarction within 12 months prior to starting study treatment
- Unstable or poorly controlled angina pectoris, including Prinzmetal variant
angina pectoris.
- History of pulmonary hypertension
- Uncontrolled infection.
-Subjects who received any of the following within the last 14 days of
initiation of study treatment:
* Major surgery (kyphoplasty is not considered major surgery).
* Use of any anti-myeloma drug therapy.
- Use of any investigational agents (with the exception of lenalidomide) within
28 days or five half-lives (whichever is longer) of treatment.
- Incidence of gastrointestinal disease that may significantly alter the
absorption of pomalidomide.
- Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
- Pregnant or breastfeeding females.
- Known human immunodeficiency virus (HIV) positivity, active infectious
hepatitis A, B or C or chronic hepatitis B or C.
- Pre-existing pulmonary, cardiac or renal impairement that prevents hydration
measures as described in the protocol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Progression free survival (PFS) from randomization, defined as time from<br /><br>randomization to progression or death from any cause which ever occur first.<br /><br>Patient still alive at the date of last contact will be censored.<br /><br>-Response rate (sCR, CR, VGPR, PR) after induction and consolidation treatment</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Response rate after 8 cycles of PCD before start of maintenance<br /><br>- Toxicity<br /><br>- Improvement of response during/after maintenance<br /><br>- Progression free survival calculated registration<br /><br>- Overall survival calculated from time of registration or from start of<br /><br>maintenance treatment, until death from any cause. Patients still alive at the<br /><br>date of last contact will be censored.<br /><br>- Quality of life as defined by the EORTC QLQ-C30 and QlQ-MY20.</p><br>