|- candidate number||5786|
|- NTR Number||NTR1825|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||19-mei-2009|
|- Secondary IDs||2008-002195-10 EudraCT number|
|- Public Title||A Phase II randomized multicenter study to assess the efficacy of lenalidomide with or without erythropoietin and granulocyte-colony stimulating factor in patients with low and intermediate-1 risk myelodysplastic syndrome.|
|- Scientific Title||A Phase II randomized multicenter study to assess the efficacy of lenalidomide with or without erythropoietin and granulocyte-colony stimulating factor in patients with low and intermediate-1 risk myelodysplastic syndrome.|
|- ACRONYM||HOVON 89 MDS|
|- hypothesis||The hypothesis to be tested is that the outcome in arm B is better than in arm A.|
|- Healt Condition(s) or Problem(s) studied||Myelodysplastic syndrome (MDS)|
|- Inclusion criteria||1. Patients with MDS classified as:|
A. RA, RARS and RAEB (with <10% myeloid blasts), CMML (with <10% myeloid blasts), according to FAB, or;
B. RA, RARS, RCMD, RCMD-RS, RAEB-1, MDS-U according to WHO, or;
C. MPD/MDS (CMML-1 according to WHO) with a WBC ≤ 12x109/l, with an IPSS ≤ 1.0.
2. 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;
3. Age ≥ 18 years;
4. WHO performance status 0-2;
5. 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;
6. Serum creatinin < 150 Ámol/l;
7. Serum billirubin < 25 Ámol/l and ASAT, ALAT and Alkaline phosphatase < 2.5 times the upper limit of normal, except if related to disease;
8. The patient must give written informed consent;
9. Negative pregnancy test within 7 days prior to start of study drug, if applicable;
10. Patient (all men, pre-menopausal women) agrees to use adequate contraceptive methods;
11. 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||1. Severe cardiac, pulmonary, neurologic, metabolic or psychiatric diseases or active malignancies;|
2. Anemia due to other causes than MDS including iron, B12 and folate deficiencies, auto-immune hemolysis and/or paroxysmal noctural hemoglobinuria (PNH);
3. Hypoplastic MDS;
4. MDS with Jak2 mutations;
5. High predictive score (score 0 or 1) to respond on standard treatment with Epo/G-CSF according to guidelines;
6. Active uncontrolled infection;
7. Absolute neutrophil count (ANC) < 0.5x10^9/l;
8. Patients dependent on platelet transfusions or with platelet counts < 25x10^9/l or patients with active bleeding;
9. Patients treated with biological response modifiers (i.e. growth factors, immunosuppressive agents and/or chemotherapy) within 1 month prior to randomization;
10. Lactating women;
11. Prior treatment with lenalidomide;
12. Prior CTCAE ≥ grade 3 allergic reaction/hypersensitivity to thalidomide;
13. Prior CTCAE ≥ grade 3 rash/blistering while taking thalidomide
14. Prior CTCAE ≥ grade 3 allergic/hypersensitivity to Epo and/or G-CSF
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jun-2009|
|- planned closingdate||30-sep-2013|
|- Target number of participants||200|
|- Interventions||Arm A: 12 cycles of lenalidomide, followed by lenalidomide maintenance cycles.
Arm B: 4 cycles of lenalidomide, followed by 4 cycles of lenalidomide +/- Epo; followed by 4 cycles of lenalidomide +/- Epo +/- G-CSF, followed by lenalidomide +/- Epo +/- G-CSF maintenance cycles.
|- Primary outcome||Hematological improvement (HI) according to IWG 2006 criteria.|
|- Secondary outcome||1. Adverse events of CTCAE ≥ grade 2;|
2. Time-to-HI and duration-of-HI;
3. Number of given treatment cycles per patient, and especially for arm B the number of patients receiving Epo and/or G-CSF;
4. Response rate (in terms of CR, PR, including cytogenetic response according to the modified response criteria of the IWG for MDS).
6. Leukemic evolution. The risk of leukemic evolution will be calculated with competing risk death without previous evolution
7. Number of transfusions of red blood cells and duration of RBC transfusion independence.
|- Timepoints||1. At entry;|
2. After each induction cycle;
3. After each maintenance cycle;
4. During follow up: every 6 months.
|- Trial web site||www.hovon.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD, PhD A.A. Loosdrecht, van de|
|- CONTACT for SCIENTIFIC QUERIES||MD, PhD A.A. Loosdrecht, van de|
|- Sponsor/Initiator ||HOVON Data Center|
(Source(s) of Monetary or Material Support)
|Amgen, Dutch Cancer Society, Johnson & Johnson, Ortho Biotech, Roche Diagnostics, Novartis, Celgene , BSP|
|- Brief summary||Study phase: Phase II.
To evaluate the efficacy of lenalidomide (Revlimid) in low/intermediate-1 risk MDS with or without treatment with Epo (NeoRecormon)/G-CSF (Neupogen).
To evaluate the safety and tolerability of lenalidomide (Revlimid) in low/intermediate-1 risk MDS with or without Epo (NeoRecormon)/G-CSF (Neupogen).
Patient population: Patients with low/intermediate-1 risk myelodysplastic syndrome.
Study design: Prospective, multicenter, open label, randomized.
Duration of treatment: Minimum of 6 months for arm A and 12 months for arm B or until relapse or disease progression; continuation thereafter if responsive. All patients will be followed until 5 years after registration.
|- Main changes (audit trail)||Exlusion criteria 4 is canceled: "4. MDS with Jak2 mutations".|
|- RECORD||19-mei-2009 - 19-aug-2013|