Maintenance treatment- To compare progression free survival between maintenance therapy with Ixazomib versus placebo, both following induction therapy with ixazomib citrate * thalidomide * low dose dexamethasone Induction treatment-To determine…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Maintenance treatment
- Progression free survival (PFS) from randomization, defined as time from
randomization to progression or death from any cause, whichever comes first
Induction treatment
- Response rate defined as sCR, CR, VGPR or PR
Secondary outcome
- Safety and toxicity as defined by type, frequency and severity of adverse
events as defined by the National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE), version 4
- PFS from registration
- Overall survival (OS) from registration, measured until death from any cause.
Patients alive will be censored at the date of last contact
- OS from randomization.
- Quality of response during maintenance, measured as improvement of response
(from start maintenance till progression)
- Time to maximum response, defined as time from registration to maximum
response
- Time to death from progression (after initial response), measured from time
of first relapse/progression
- Time to next treatment
- PFS from the start of second line therapy
- Quality of life as defined by the EORTC QLQ-C30 and QLQ-MY20 definitions.
- Second Primary Malignancies
Background summary
Standard of care in Europe for newly diagnosed MM patients who are not eligible
for autologous stem cell transplantation is melphalan-prednisone-bortezomib.
Hematological toxicity and increased rate of second primary malignancies with
alkylating agents justifies the investigation of a triplet combination therapy
omitting alkylating agents. A triplet combination without alkylating agents
combining an IMiD (thalidomide or lenalidomide), a proteasome inhibitor
(bortezomib) and corticosteroids have been found to be very effective indeed.
In view of In view of a high incidence of peripheral neuropathy in the current
protocol bortezomib will be replaced with the oral proteasome inhibitor
ixazomib. Importantly, this is an oral regimen, especially being convenient in
an elderly population. The hypothesis is that the response rate will be
superior, with less hematological and painful neural toxicity as compared to
standard therapy. In addition, a role for maintenance therapy with bortezomib
has been suggested in non-head to head comparisons. Therefore, the efficacy of
Ixazomib maintenance therapy will be investigated by randomizing maintenance
treatment with Ixazomib versus placebo.
Study objective
Maintenance treatment
- To compare progression free survival between maintenance therapy with
Ixazomib versus placebo, both following induction therapy with ixazomib citrate
* thalidomide * low dose dexamethasone
Induction treatment
-To determine overall response* rate of induction therapy with ixazomib citrate
* thalidomide * low dose dexamethasone
* overall response will be defined as (stringent) complete response, very
good partial
response and partial response
Study design
Phase II trial
Intervention
Induction treatment with Ixazomib, Thalidomide and Dexamethasone.
Following induction therapy half of the patients will receive 4 mg of Ixazomib
capsules as a maintenance therapy until progression and the other half of
patients will receive placebo capsules as a maintenance therapy until
progression
Study burden and risks
The burden will be that following induction therapy, maintenance therapy will
be given until progression. Although a benefit with respect to prolongation of
PFS is expected, the extent is currently unknown. Patients may suffer from side
effects, although these are generally mild with ixazomib citrate. Moreover, 50%
of patients receive a placebo. There are no additional procedures required as
compared to standard care. Patients will only be requested to participate in
Quality of Life studies and will be asked to give extra blood and marrow for
future research.
VUMC, HOVON Centraal Bureau, De Boelelaan 117
Amsterdam 1081 HV
NL
VUMC, HOVON Centraal Bureau, De Boelelaan 117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Previously untreated patients with a confirmed diagnosis of symptomatic
multiple myeloma according to IMWG criteria
- Measurable disease according to the IMWG criteria (If plasmacytoma is the
only measurable parameter, the patient is not allowed to be included in the
study, because of difficult response evaluation).
- Age * 66 years or patients * 65 years not eligible for ASCT
- WHO performance status 0-3 for patients <75 years and WHO performance status
0-2 for patients * 75 years
- Absolute neutrophil count (ANC) * 1.0 x109/l and platelet count * 75x109/l ,
unless related to bone marrow infiltration by malignant plasmacells .
- Written informed consent.
- Patient gives consent for extra bone marrow and blood sampling.
- Negative pregnancy test at study entry or at least 1 year post-menopausal or
surgically sterile before study entry
- Patients must use adequate contraception as specified in the protocol (all
men and all women of childbearing potential)
Exclusion criteria
- Known allergy to any of the study medications, their analogues, or excipients
in the various formulations of any agent
- Systemic AL amyloidosis
- Polyneuropathy, grade 3 or higher or grade 2 with pain on clinical
examination during the screening period
- Evidence of current uncontrolled cardiovascular conditions, including
uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic
congestive heart failure, unstable angina, or myocardial infarction within the
past 6 months
- Severe pulmonary dysfunction (Modified Medical Research Counsil dyspnea scale
classification III-IV)
- Significant hepatic dysfunction (total bilirubin * 1.5 x ULN or transaminases
* 3 times normal level) except patients with Gilbert*s syndrome as defined by >
80% unconjugated bilirubin
- Creatinine clearance <30 ml/min or Calculated Glomerular Filtration Rate
[ml/min/1.73m2] <30
- Systemic treatment, within 14 days before the first dose of ixazomib, with
strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine,
phenytoin, phenobarbital), or use of Ginkgo biloba or St. John*s wort.
- Pre-treatment with cytostatic drug, IMIDs or proteasome inhibitors.
Radiotherapy or a short course of steroids (e.g. 4 day treatment of
dexamethasone 40 mg/day or equivalent) are allowed. Radiotherapy should not be
given within 14 days before enrollment. In case of radiotherapy, if the
involved field is small, 7 days will be considered a sufficient interval
between treatment and administration of the ixazomib citrate
- Not able and/or not willing to use adequate contraception
- Female patients who are lactating or have a positive serum pregnancy test
during the screening period,
- Major surgery within 14 days before enrollment.
- Central nervous system involvement.
- Ongoing or active systemic infection, active hepatitis B or C virus
infection, or known human immunodeficiency virus (HIV) positive.
- Known GI disease or GI procedure that could interfere with the oral
absorption or tolerance of ixazomib citraat including difficulty swallowing.
- Diagnosed or treated for another malignancy within 2 years before study
enrollment or previously diagnosed with another malignancy and have any
evidence of residual disease. Patients with nonmelanoma skin cancer or
carcinoma in situ of any type are not excluded if they have undergone complete
resection.
- Participation in other clinical trials, including those with other
investigational agents not included in this trial, within 21days of the start
of this trial and throughout the duration of this trial.
- Any serious medical or psychiatric illness, or familial, sociological and
geographical condition potentially hampering compliance with the study protocol
and follow-up schedule
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003266-14-NL |
| CCMO | NL45340.029.14 |
| OMON | NL-OMON29252 |