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…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
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 treatment
Secondary outcome
- Response rate after 8 cycles of PCD before start of maintenance
- Toxicity
- 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.
Background 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.
Study objective
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 defined as response rate (sCR, CR, VGPR, PR) 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
Study design
Fase II trial
Intervention
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 may
receive high-dose Melphalan. and autologous stem cell reinfusion (autoSCT) of
cells already stored during initial treatment. 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.
Study burden and risks
The combination of Pomalidomide, Carfilzomib and Dexamethason may be useful in
the treatment of relapsed MM patients. In order to study the safety and
efficacy of this combination it is required to include patients who have
relapsed MM. The knowledge from this study may be of advantage to this group of
patients in the future.
The majority of the investigations performed in this study do not differ from
the usual standard of care for this patient category. Exceptions are that at
the beginning of the study patients will be requested to provide extra blood
and bone marrow aspirate for analysis (this does not require extra punctures);
extra blood and bone marrow will be collected during the first induction cycle;
patients will also be asked to complete Quality of Life Questionnaires at
regular intervals and to protect unborn children women of childbearing
potential will be asked to regularly perform a pregnancy test.
There is a possibility that by taking part in the study patients will
experience side effects from the medications under investigation.
The treating physician will always safeguard the health and best interest of
the patients and furthermore an independent physician is available to provide
independent advice to the patients.
HOVON Centraal Bureau, VUMC, De Boelelaan 1117
Amsterdam 1081 HV
NL
HOVON Centraal Bureau, VUMC, De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- 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.
Exclusion criteria
-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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003265-34-NL |
| CCMO | NL45339.078.14 |