|- candidate number||22536|
|- NTR Number||NTR5349|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||4-aug-2015|
|- Secondary IDs|| 2014-664/NL 45339.078.14. MEC/CCMO|
|- Public Title||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
|- Scientific Title||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.|
|- ACRONYM||HOVON 114 MM|
|- hypothesis||This study aims to assess the efficacy and safety of induction and consolidation therapy with Carfilzomib, Pomalidomide and Dexamethasone in subjects with relapsed or refractory multiple myeloma (MM)
after prior first-line treatment in the EMN02/HO95 trial who are refractory to Lenalidomide
Furthermore, the efficacy of maintenance therapy with Pomalidomide versus Pomalidomide plus Dexamethasone will be determined.
|- Healt Condition(s) or Problem(s) studied||Multiple myeloma|
|- 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 ¡Ý 18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol
- Documented diagnosis of multiple myeloma and measurable disease
(serum M-protein ¡Ý 10 g/L or urine M-protein ¡Ý 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
- All subjects must agree to refrain from donating blood while on study
drug and for 28 days after discontinuation from this
- 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 ¡Ý 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 ¡Ý Grade 3 rash during prior thalidomide or
lenalidomide or bortezomib therapy).
- Peripheral neuropathy ¡Ý 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 ¡Ü 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
- 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
- Any serious medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subjects from signing the informed
- 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
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||30-jul-2015|
|- planned closingdate||30-jul-2025|
|- Target number of participants||222|
|- Interventions||The following treatments will apply:|
Patients who progess from EMN02/HO95, who were treated
with standard dose melphalan (VCD, followed by VMP,
followed by yes/no VRD consolidation, followed by
lenalidomide maintenance) will be treated with 4 cycles of
PCd induction (Pomalidomide Carfilzomib dexamethasone).
After induction they will receive HighDose Melphalan and
autologous stem cell reinfusion (autoSCT) of cells already
stored during initial treatment, if possible. Following
hematologic recovery, these patients will receive 4 cycles of
consolidation treatment with PCd.
Patients who progress from EMN02/HO95, who were
treated with High Dose Melphalan (VCD, followed by
HDM+autoSCT followed by yes/no VRD consolidation,
followed by lenalidomide maintenance) will be treated with 4
cycles of PCd induction, followed by 4 cycles of consolidation treatment with PCd.
All patients who have completed the re-induction and
consolidation treatment will be randomized for maintenance
treatment with pomalidomide alone or pomalidomide plus
dexamethasone until progression of disease.
|- Primary outcome||- Progression free survival (PFS) from randomization, defined as time
from randomization to progression or death from any cause which ever
occur first. Patient still alive at the date of last contact will be censored.|
- Response rate (sCR, CR, VGPR, PR) after induction and consolidation
|- Secondary outcome||-Response rate after 8 cycles of PCD before start of maintenance|
-Improvement of response during/after maintenance
-Progression free survival calculated registration
-Overall survival calculated from time of registration or from start of
maintenance treatment, until death from any cause. Patients still alive at
the date of last contact will be censored.
-Quality of life as defined by the EORTC QLQ-C30 and QlQ-MY20.
|- Timepoints||- At entry|
− After induction treatment cycle 2 and 4
− After High-dose Melphalan and autologous stem cell transplantation (if applicable)
− After consolidation treatment cycle 2 and 4
− After every 2nd maintenance cycle until progression
− During follow up every 2 months until progression/relapse. Thereafter every 6 months until 8 years after registration.
|- Trial web site||www.hovon.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. P. Sonneveld|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. P. Sonneveld|
|- Sponsor/Initiator ||Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)|
(Source(s) of Monetary or Material Support)
|Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON), Dutch Cancer Society, Onyx Pharmaceuticals, Celgene |
|- Brief summary||This trial will try to evaluate the efficacy of the combination of Pomalidomide, Carfilzomib and low dose Dexamethasone
for induction and consolidation in subjects with relapsed or refractory multiple myeloma after prior first-line treatment in the
EMN02/HO95 trial and who are refractory to Lenalidomide and Bortezomib.
Despite the use of high-dose chemotherapy and autologous stem cell transplantation, Multiple Myeloma remains
incurable. The 5-year survival rate for patients with multiple myeloma among patients treated with conventional
chemotherapy is 25%, while with intensified therapy this may increase to more than 50 %. In the majority of subjects the
disease follows a relapsing course, regardless of treatment regimen or initial response to treatment. Novel agents are
urgently needed to improve the treatment results of this disease.|
|- Main changes (audit trail)|
|- RECORD||4-aug-2015 - 25-aug-2015|