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Clinical picture: MM (Multiple Myeloom)
Trial: HOVON 114 MM
News
1. Overview
Study details
2. Patient eligibility criteria
3. Registration (& randomization) of patients
4. Participating parties
5. Participating sites
6. Instruction videos
7. Download documentation / forms
News
HO114 news
04-07-2016
Implementatie nieuwe versie protocol v 5 dd. 23032016
Nieuwe versie van het registratie CRF beschikbaar (v3 30JUN16)
12-07-2016
Kleine correctie in het registratie CRF v3 (ontbrekende invulvelden toegevoegd voor inclusiecriteria nr. 2 en 3)
26-07-2016
Nieuwe versie registratie en randomisatie CRF v4 beschikbaar (toevoeging randomisatie formulier)
1. Overview
Summary
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 progression after prior 1st line treatment with Lenalidomide and Bortezomib.
The European Intergroup Trial of the European Myeloma Network EMN
(EMN11/HO114)
Status
open
Members
Participating groups: HOVON, GIMEMA, CEMSG, CMG, NSMG, GR, TR
Uitleg patienten informatie
Beste patient, hieronder vindt u een link naar de patienten informatie die beschikbaar is voor deze studie. Mochten er vragen zijn, dan kunt u deze het beste stellen aan uw behandelend arts.
Study details
Type of study
Prospective randomized Phase II study
Echelon level
Limited site selection
Type of monitoring for this study
Site evaluation visits
Target number of patients
222
Current number of patients
0
Approved by
central EC NL Erasmus MC
CCMO
central EC BE ZNA
FAGG
Study objectives
Primary objectives
• Evaluate the efficacy defined as PFS of pomalidomide maintenance plus dexamethasone versus pomalidomide maintenance in patients who responded (≥ PR) to the combination of pomalidomide (POM), carfilzomib (CAR) and low dose dexamethasone (LD-DEX) for induction and consolidation.
• Evaluate efficacy of the combination of pomalidomide (POM), carfilzomib (CAR) and low dose dexamethasone (LD-DEX) for induction and consolidation in subjects with relapsed or refractory multiple myeloma (MM) after prior first-line treatment in the EMN02/HO95 trial who are refractory to Lenalidomide and/or Bortezomib. This objective will be investigated in patients who have or have not received a prior autologous transplant.
Secondary objectives
• Evaluate the response rate ( after 8 cycles of PCd) before the start of maintenance.
• Evaluate the safety and tolerability of the combination of pomalidomide, carfilzomib and low dose dexamethasone in subjects with relapsed or refractory multiple myeloma.
Exploratory
• Evaluation of biomarkers, including baseline markers predictive of response to pomalidomide combined with carfilzomib and dexamethasone.
• Evaluate the quality of life
Evaluate the gene expression profiles and SNPs in relation to the treatment outcomes and side-effects
2. Patient eligibility criteria
Inclusion criteria
• Included in EMN02/HO95 trial
• 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).
• At least prior anti-myeloma regimen according to the EMN02/HO95 trial and documented progression or refractory multiple myeloma as per the IMWG uniform response criteria (Durie, 2006) during or after the last anti-myeloma regimen. Induction therapy followed by autologous stem cell transplant (AutoSCT) and consolidation/ maintenance will be considered as one regimen.
• Patients who have never achieved a response better than PD after at least 2 cycles of lenalidomide containing therapy or who progressed whilst on treatment.
• 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.
• 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.
Exclusion criteria
• 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 (this includes ≥ Grade 3 rash during prior thalidomide or lenalidomide or bortezomib therapy).
• 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 pointe.
• 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.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form.
• 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 at section 9.5.
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
3. Registration (& randomization) of patients
Registration
Central registration at EMN Data Center
University of Torino
Via Genova 3
10126 Torino, Italy
tel. +39 .011 6336107
fax. +39 011 6334301
fax +39 011 6963737
Registration criteria
The following information will be requested:• Protocol number
• Institution name
• Name of caller/responsible investigator
• Sex
• Date of birth
• Date written informed consent
• Specific items patient gives consent for (see ICF)
• Eligibility criteria
• Criteria for measurable disease and CRAB criteria
4. Participating parties
Principal Investigator(s)
Prof. Dr. P. Sonneveld (Erasmus MC - Centrum)
Co-Investigator(s)
Prof. Dr. H.M. Lokhorst (VUMC)
Prof. A. Palumbo (Osp. G. Battista Le Molinette -V.Genova)
Coordinating Investigator(s)
Prof. Dr. M. Beksac (Ankara University Hosp. Cebeci Hastanesi)
Dr. M.A. Dimopoulos (Regional General Hospital Alexandra)
Prof. Dr. R. Hajek (University Hospital Ostrava)
Prof. Dr. H. Ludwig (Wilhelminenspital)
Dhr. Dr. K.L. Wu (ZNA Stuivenberg)
Statistician(s)
Dhr. K. Nasserinejad (Erasmus MC - Centrum)
Monitor - Site Evaluation Visits
Mw. I. Enthoven (Erasmus MC - Daniel)
Mw. W.M Keller (Erasmus MC - Daniel)
Mw. J. Kromme (Erasmus MC - Daniel)
Other functions
Central Coordinator - Molecular Diagnostics - Dhr. Dr. M. van Duin (Erasmus MC - Daniel)
Principal investigator
P. Sonneveld (p.sonneveld@erasmusmc.nl)
Coordinating investigator(s)
H. Ludwig (CEMSG) (heinz.ludwig@wienkav.at)
H.Lokhorst (HOVON) (h.lokhorst@vumc.nl)
A. Palumbo (GIMEMA) (appalumbo@yahoo.com)
K. Wu (HOVON) (kalung.wu@zna.be)
M. Hanson (Markus.Hansson@med.lu.se)
M. Dimopoulos (mdimop@med.uoa.gr)
R. Hajek (roman.hajek@fno.cz)
M. Beksac (beksac@medicine.ankara.edu.tr)
Trial manager
T. Gussinklo (a.gussinklo@erasmusmc.nl)
Central data management
EMN Data Center
Other functions
Please contact monitors at hdcmonitorteam@erasmusmc.nl
5. Participating sites
* Please note that if TOP is not used to register patients for a study, the number of patients shown is zero.