Primary objective- To evaluate the efficacy of lenalidomide (RevlimidTM) in low/int-1 risk MDS with or without a treatment with Epo (NeoRecormonTM)/G-CSF (NeupogenTM) in terms of hematological improvement (HI) as defined by the modified response…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint
- Hematological improvement (HI) according to IWG 2006 criteria
Secondary outcome
Secondary endpoints
- Adverse events of CTCAE >= grade 2
- Time-to-HI and duration-of-HI (i.e. time from HI to relapse after HI or death
from any cause)
- Number of given treatment cycles per patient, and especially for arm B the
number of patients receiving Epo and/or G-CSF
- Response rate (in terms of CR, PR, including cytogenetic response according
to the modified response criteria of the IWG for MDS
- Progression-free-survival, i.e. time from registration to relapse, disease
progression or death from any cause
- Leukemic evolution. The risk of leukemic evolution will be calculated with
competing risk death without previous evolution
- Number of transfusions of red blood cells and duration of RBC transfusion
independence
Background summary
In low/int-1 risk MDS no current standard treatment programs are available
except for Epo/G-CSF in selected cases based on the predictive model of
response to Epo/G-CSF (E. Helstrom-Lindberg; ELN 2008 recommendations;
www.leukemia-net.org), in accordance with guidelines of several MDS working
parties [23,26,27]. Based on new insights in the pathobiology of low/int-1 risk
MDS new targets for therapy are emerging interfering with apoptosis of
hematopoietic progenitors and interfering with the complex interactions of the
microenvironment, the immune system and (leukemic)- progenitor cells. In this
respect, lenalidomide with the pleiotropic effects including erythropoietic
remitting activity in low/int-1 risk MDS is of particular interest. Epo/G-CSF
might further potentiate the effects of lenalidomide by interfering with
apoptotic signalling of hematopoietic precursor cells as well as with the
optimisation of immune effector cell function. This might have impact on the
survival of erythropoietic progenitor cells and their progeny with clinical and
hematological improvement of patients with MDS. With respect to safety
concerns, it is not likely that the addition of Epo/G-CSF to lenalidomide may
induce an increased risk in hematological and/or non-hematological toxicities.
Study objective
Primary objective
- To evaluate the efficacy of lenalidomide (RevlimidTM) in low/int-1 risk MDS
with or without a treatment with Epo (NeoRecormonTM)/G-CSF (NeupogenTM) in
terms of hematological improvement (HI) as defined by the modified response
criteria of the IWG for MDS
Secondary objectives
- To evaluate the safety and tolerability of lenalidomide (RevlimidTM) in
low/int-1 risk MDS with or without Epo (NeoRecormonTM)/G-CSF (NeupogenTM)
- Time-to-HI and duration-of-HI
- Aantal gegeven kuren en aantal patienten dat Epo en/of G-CSF krijgt
- The number of given treatment cycles per patient and for arm B the number of
patients receiving Epo and/or G-CSF
- The response rate (in terms of CR, PR, including cytogenetic response
according to the modified response criteria of the IWG for MDS
- Progression-Free-Survival (i.e. time from registration to disease
progression, including progression to leukemia, or death from any cause)
- Transfusion requirements of red blood cells
Study design
Phase II, multicenter, with randomisation between lenalidomide and lenalidomide
+ Epo/G-CSF in 200 patients with low or intermediate-1 risk myelodysplastic
syndrome..
Intervention
For arm A: lenalidomide (Revlimid*) 10mg p.o./day 1-21 in a 28-day cycle.
Patients will receive at least 6 cycles. If responsive, patients may continue
treatment until loss of HI or progression of disease. For arm B: lenalidomide
(Revlimid*)10mg p.o./day 1-21 in a 28-day cycle. After 4 cycles addition of
erythropoietin (NeoRecormon*) s.c., 1x/wk 30000 to 60000IE depending on
response. After 8 cycles, dependent on HI, G-CSF(Neupogen*) s.c, 3x/wk
300/480µg is added to according to current standard and validated treatment
schedules. Patients will receive at least 12 cycles. If responsive, patients
may continue treatment until loss of HI or disease progression.
Study burden and risks
No additional risks associated with participation of the study are yet known.
To monitor either response or disease progression during therapy, every 3 month
an additional bone marrow puncture is necessary. In general, this examination
is not aggravating.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Patients with MDS classified as:
* RA, RARS and RAEB (with <10% myeloid blasts), CMML (with <10% myeloid blasts), according to FAB or
*RA, RARS, RCMD, RCMD-RS, RAEB-1, MDS-U according to WHO or
*patients with MPD/MDS (CMML-1 according to WHO) with a WBC <= 12x109/l with an IPSS <= 1.0
- Hb <= 6.2 mmol/l (10.0 g/dl) or Hb <= 7.2 mmol/l and ANC <= 1.0x109/l or red blood cell transfusion dependent
- Age >= 18 years
- WHO performance status 0-2
- Patient not previously treated with Epo/G-CSF, or
failure of response or relapse after hematological improvement or disease progression to maximal RAEB-1 after previous therapy with Epo/G-CSF
- Serum creatinin < 150 µmol/l
- Serum billirubin < 25 µmol/l and ASAT, ALAT and Alkaline phosphatase < 2.5 times the upper limit of normal, except if related to disease
- The patient must give written informed consent
- Negative pregnancy test within 7 days prior to start of study drug, if applicable.
- Patient (all men, pre-menopausal women) agrees to use adequate contraceptive methods.
- Serum erythropoietin level
*> 200 U/l or
*<= 200 U/l if failure of response or loss of hematological improvement or disease progression to maximal RAEB-1 after prior standard therapy with Epo/G-CSF;
Epo/G-CSF should be stopped at least 1 month before randomization.
Exclusion criteria
- Severe cardiac, pulmonary, neurologic, metabolic or psychiatric diseases or active malignancies.
- Anemia due to other causes than MDS including iron, B12 and folate deficiencies, auto-immune hemolysis and/or paroxysmal noctural hemoglobinuria (PNH)
- Hypoplastic MDS
- High predictive score (score 0 or 1) to respond on standard treatment with Epo/G-CSF according to guidelines
- Active uncontrolled infection
- Absolute neutrophil count (ANC) < 0.5x109/l
- Patients dependent on platelet transfusions or with platelet counts < 25x109/l or patients with active bleeding
- Patients treated with biological response modifiers (i.e. growth factors, immunosuppressive agents and/or chemotherapy) within 1 month prior to randomization
- Lactating women
- Prior treatment with lenalidomide
- Prior CTCAE >= grade 3 allergic reaction/hypersensitivity to thalidomide
- Prior CTCAE >= grade 3 rash/blistering while taking thalidomide
- Prior CTCAE >= grade 3 allergic/hypersensitivity to Epo and/or G-CSF
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 | EUCTR2008-002195-10-NL |
| CCMO | NL25632.029.08 |
| Other | NTR1825 & LN_NN_2009_392 |