* To determine the efficacy of bortezomib plus dexamethasone induction therapy followed by HDM and auto-SCT in patients with newly diagnosed AL amyloidosis who are 18-70 years inclusive.* To asses the safety of bortezomib plus dexamethasone as…
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Hematological CR rate 6 months after auto-SCT. Patients are considered a
success if they received HDM and auto-SCT and are in CHR at 6 months, all other
patients are considered a failure.
Secondary outcome
* Overall survival measured from the time of registration. Patients still alive
or lost to follow up ace censored at the day they were last known to be alive
* Progression Free Survival, (hematological), i.e. time from registration until
hematological progression, relapse or death, whichever occurs first.
* Hematological response rate rate after induction therapy
* Response Rate, hematological and organ
* Time to response, hematological and organ
* Duration of response, hematological and organ
* Time to next AL amyloidosis therapy
* Safety (type, frequency, and severity of adverse events (AE) and relationship
of AE to study drug
* Exploratory assessment of multiparameter flow cytometry quantification of
bone marrow plasma cells and change in amyloid deposition in abdominal fat
aspiration samples
* Evaluation of prognostic factors for survival included in the hematological
and organ response criteria
Background summary
The aim of the current study is to investigate the efficacy of induction
treatment consisting of bortezomib and dexamethasone followed by HDM and
auto-SCT to improve the hematological response rate and especially the CHR of
patients with de novo AL amyloidosis. Considering the potent effect in relapsed
AL amyloidosis patients and the improvement in response rates achieved when
used as the first line treatment of MM patients, it is expected that the use of
bortezomib will also improve the response rate in first line treatment of AL
amyloidosis patients.
With the use of induction therapy the TRM of the auto-SCT procedure is < 5% and
the hematological response after the treatment is long-lasting. Because
hematological response rate is closely related with survival in this patient
population a better response rate will translate into better overall survival.
Study objective
* To determine the efficacy of bortezomib plus dexamethasone induction therapy
followed by HDM and auto-SCT in patients with newly diagnosed AL amyloidosis
who are 18-70 years inclusive.
* To asses the safety of bortezomib plus dexamethasone as induction treatment
followed by HDM and auto-SCT in patients with newly diagnosed AL amyloidosis
who are 18-70 years inclusive.
Study design
This is a multi-center, open label, 1 arm phase II study.
Intervention
Treatment consists of bortezomib and dexamethasone followed by stem cell
mobilization, HDM and auto-SCT.
Study burden and risks
Patients are exposed to bortezomib and therefore to the side effects of the
drug such as peripheral polyneuropathy, gastro-intestinal complaints and
thrombocytopenia. If informed consent is given for participation in the
experimental studies patients will undergo 4 additional abdominal fat
aspiration procedures
de Boelelaan 1117
amsterdam 1007 MB
NL
de Boelelaan 1117
amsterdam 1007 MB
NL
Listed location countries
Age
Inclusion criteria
* Biopsy proven, systemic, untreated AL amyloidosis requiring systemic chemotherapy,
* Age 18 -70 years inclusive at the time of signing the informed consent form,
* Measurable plasma cell dyscrasia, defined as a detectable M-protein with serum electrophoresis and/or level of involved FLC> 50 mg/L,
* Life expectancy > 3 months,
* WHO performance status 0-2,
* NYHA stage 1-2,
* Negative pregnancy test at inclusion for women of childbearing potential,
* Written informed consent.
Exclusion criteria
* Multiple Myeloma stage II and III (Durie and Salmon),
* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form,
* Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule,
* Previous treatment for plasma cell dyscrasia
* Pregnant or breast feeding females.
* Presence of other active malignancy or a history of active malignancy during the past 5 years, with the exception of nonmelanoma skin cancer, stage 0 cervical carcinoma, or treated early-stage prostate cancer provided that prostate-specific antigen is within normal limits,
* Hypersensitivity to boron or mannitol,
* Uncontrolled infection,
* Symptomatic othostatic hypotension defined as a decrease in systolic blood pressure on standing of >20mmHg combined with symptoms like dizziness, cerebral and/or cardial ischemia,
*NT pro BNP level > 5000 pg/ml and Troponin T> 0.06 microgram/l (not high senstitivity assay) or NT proBNP level > 5000 pg/ml and Troponin I > 2 times ULN
* Symptomatic effusions, defined as pleural effusion or ascites needing drainage therapy,
* Positive for HIV or infectious hepatitis, B or C,
* Bilirubin > 2x upper limit of normal,
* Creatinin clearance < 30 ml/min (after rehydration),
* Absolute neutrophil count < 1.0 × 109/L,
* NCI CTCAE grade peripheral sensory neuropathy > grade 2,
* NCI CTCAE grade peripheral sensory neuropathy > grade 1 in the presence of neuropathic pain,
*NCI CTCAE grade peripheral motor neuropathy > grade 2
* Concurrent diagnosis of B-cel NHL or B-CLL,
* Previous organ transplantation.
* Unwilling or unable to use adequate contraception
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 | EUCTR2010-021445-42-NL |
| CCMO | NL33641.041.10 |
| Other | NL33641.041.10 |