Currently, there are no curative treatment options for patients with Waldenstrom*s macroglobulinemia (WM) and there is no consensus on standard first line or relapse treatment. The proteasome inhibitor bortezomib has shown efficacy in WM, but is…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For the phase I part: to establish the recommended phase II dose (RP2D) for the
combination of oral ixazomib citrate and dexamethasone in patients with WM.
For the phase II part: To assess the efficacy (overall response rate) of oral
ixazomib citrate in combination with rituximab and dexamethasone (IRD
schedule).
Secondary outcome
Secondary Study Objectives (for the phase II part):
- To assess the safety of oral ixazomib citrate in combination with rituximab
and dexamethasone, followed by rituximab maintenance for 2 years, with special
emphasis on neurotoxicity, infections and the incidence of IgM flare requiring
plasmapheresis
- To assess the feasibility of oral ixazomib citrate in combination with
rituximab and dexamethasone, defined as percentage of patients who complete the
full treatment course (at least 6 cycles of induction treatment and 2 years of
maintenance treatment)
- To assess the effect of 2 cycles of oral ixazomib citrate and dexamethasone
(before rituximab is added) on M-protein levels
-To assess the improvement of response during rituximab maintenance
- To assess the effect of the treatment on patient reported outcomes (quality
of life (QoL))
- To perform an exploratory analysis of prognostic markers and markers of
disease activity
- To study in vivo the effect of treatment with an oral proteasome inhibitor on
sorted WM B- cells and plasma cells from the bone marrow
Background summary
See objective of the study
Study objective
Currently, there are no curative treatment options for patients with
Waldenstrom*s macroglobulinemia (WM) and there is no consensus on standard
first line or relapse treatment. The proteasome inhibitor bortezomib has shown
efficacy in WM, but is associated with a high incidence of
neurotoxicity. The oral proteasome inhibitor ixazomib citrate has been shown to
induce very little neurotoxicity in patients with multiple myeloma and is
therefore an attractive drug to test also in patients with WM.
Study design
Phase I/ II trial.
The phase I trial will be carried out with 2 dose levels of ixazomib citrate. A
lower dose level is anticipated in case the starting dose level is not
feasible. The phase II trial is an open label, non-randomized phase II study
according to a Simon*s two stage minimax design.
Intervention
All patients will receive 8 cycles of induction treatment with ixazomib
citrate, rituximab (only cycles 3 to 8) and dexamethasone, followed by 2 years
of maintenance treatment with rituximab once every 3 months.
Study burden and risks
Currently, there is no standard treatment for patients with relapsed WM.
Rituximab and dexamethasone are effective drugs in WM. The proteasome inhibitor
bortezomib has shown efficacy in WM, but is associated with a high incidence of
neurotoxicity. Ixazomib citrate is a novel oral proteasome inhibitor with a
more favorable toxicity profile in patients with MM compared to bortezomib,
including a low rate of neurotoxicity.
The hypothesis is that treatment with the combination ixazomib citrate,
rituximab and dexamethasone will be effective in patients with relapsed WM with
good tolerability.
Risks for the patient relate to drug specific side-effects, in particular the
risk of skin toxicity and gastrointestinal toxicity. Extra blood will be drawn
for side studies, however patients will not undergo additional venapunctures
since this will be done at timepoints when blood is drawn for regular checks.
In patients giving informed consent an extra bone marrow puncture will be
performed at 48 hours after the first ixazomib citrate dose and after 4 cycles
of induction.
HOVON Centraal Bureau, VUMC, De Boelelaan 1117
Amsterdam 1081HV
NL
HOVON Centraal Bureau, VUMC, De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
- diagnosis of relapsed or progressive WM
- age >=18 years
- WHO performance status 0-2
- >=1 prior lines of treatment
- negative pregnancy test at study entry
- male and female patients using adequate contraceptive methods until 3 months
after last dose of study drug
- written informed consent
Exclusion criteria
- bortezomib or rituximab refractory
- severe cardiac, pulmonary or hepatic dysfunction
- systemic treatment with strong CYP1A2 inhibitors within 14 days of first dose
ixazomib citrate
- know HIV positivity
- Bing Neel Syndrome
- breastfeeding
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 | EUCTR2013-002711-94-NL |
| CCMO | NL45714.018.14 |