Track topics on Twitter Track topics that are important to you
The study is aimed to treat low-risk MDS patients,who are dependent on red-blood cell transfusion due to disease-related anemia, and who have a proven resistance towards treatment with erythropoetin-stimulating agents (ESA). The study randomizes patients to receive a treatment with the demethylating agent 5-azacytidine alone or in combination with an ESA. The study thus evaluates, if efficacy of 5-azacytidine, notably on the red-blood cell transfusion-dependence is comparable/inferior to a combination treatment with azacitidine and an ESA (that is if 5-azacytidine can overcome the resistance towards ESA). Being a phase II study, the study assesses, duration of erythroid response, overall survival and time to progression as well as toxicity.
Phase II Study of Azacitidine (Vidaza®) Combined to Epoetin Beta (NeoRecormon®) in IPSS Low-risk and Intermediate-1 MDS Patients, Resistant to ESA
The Primary Endpoint of this study is to determine the major erythroid response rate after 6 courses, assessed according to IWG 2000 criteria.
The Secondary Endpoints are to determine the percentage of major HI-E and minor HI-E after 4 and 6 courses according to IWG 2000, the HI-E IWG 2006 criteria, the duration of erythroid response, the red blood cell transfusion independence at 4 and 6 months, the overall survival and time to IPSS progression and the toxicity (NCI-CTAE).
The trial will enroll 98 patients (49 patients per arm)
Treatment in arm A:
Azacitidine 75mg/sqm SQ per day for 5 days every 28 days for 6 courses Dosing of each subsequent course will be adapted according to extrahematological toxicity and cytopenias.
In responders after 6 courses of azacitidine according to IWG 2000 criteria (both minor and major erythroid responses of HI-E) 12 identical additional maintenance courses will be delivered every 28 days, unless relapse occurs (according to IWG 2000 criteria).
Treatment in arm B:
• Azacitidine 75mg/sqm SQ per day for 5 days every 28 days for 6 courses.
(dosing of each subsequent course will be adapted according to extra hematological toxicity and cytopenias) AND
• Epoetin beta : 60000U weekly SQ injections Dosing of epoetin beta will be adapted according to current ASH-ASCO guidelines and black box warning of epoetin beta. Epoetin beta therapy may therefore be interrupted, in case of response to azacitidine, as soon as a hemoglobin level of 12g/dl is achieved on two sequential bimonthly blood count measurements.
A 40% dose reduction of epoetin beta will be required if:
- Hb level rise of 1 g/dl is observed within two weeks
- Hb level exceeds 11g/dl
In responders after 6 courses of azacitidine + epoetin beta, according to IWG 2000 criteria (both minor and major erythroid responses of HI-E) 12 identical additional maintenance courses of azacitidine will be delivered every 28 days, unless relapse occurs (according to IWG 2000 criteria) Epoetin beta will be administered as described above.
In both arms, each subsequent course will be delivered
- In absence of persistent grade >2 non-hematological toxicity
- In absence of rehospitalisation for severe bleeding, infection or febrile neutropenia and non-hematological toxicity following the previous course
- If neutrophil counts are > 1G/l or > 50% of baseline neutrophil counts
- If platelets are > 75G/l or > 50% of baseline platelets counts
In case of persistent cytopenia, blood counts will be at least checked every 2 weeks, and the next course delayed until resolution of cytopenia, as defined above.
In case of persistence of cytopenia beyond day 56 of the preceding course, an new evaluation of the disease, using clinical examination, blood and bone marrow examinations +/- cytogenetics will be mandatory before eventually pursuing azacitidine at lower dosing levels.
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Azacitidine, Epoetin beta
Groupe Francophone des Myelodysplasies
Published on BioPortfolio: 2014-08-27T03:17:55-0400
The purpose of this study is - To evaluate the efficacy of association of Erythropoetin (Neorecormon) and ATRA in patients with low risk myelodysplastic syndromes - To e...
This trial is designed to explore a modified dose and schedule of azacitidine in order to more effectively address the needs of patients with low-risk myelodysplastic syndromes (MDS), i.e....
The objectives of this trial are to evaluate the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics and preliminary efficacy of volasertib in two dosing schedules of intr...
The hypothesis of this study is that 5-aza and lenalidomide act synergistically in MDS and AML patients with chromosomal abnormalities involving monosomy 5 or del5q. Therefore, this phase ...
This is a Phase 1b, dose-ranging, open-label, multicenter study designed to evaluate the safety, pharmacokinetics, and efficacy of venetoclax as a single-agent and in combination with azac...
Relapse is the main cause of treatment failure after allogeneic stem cell transplant (alloSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Injectable azacitidine can improve p...
Azacitidine (AZA) is a nucleoside analog used for treatment of myelodysplasia and the prediction of AZA responsiveness is important for the therapy management.
Thrombocytopenia is among the strongest predictors of decreased survival for patients with myelodysplastic syndromes (MDS) across all prognostic risk groups. The safety and efficacy of CC-486 (oral az...
Relapsing polychondritis (RP) is a rare autoimmune disorder, and myelodysplastic syndrome (MDS) is accompanied by RP at variable rates. Herein, we report a case with RP and MDS who responded dramatica...
Clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either MYELODYSPLASTIC SYNDROMES or MYELOPROLIFERATIVE DISORDERS.
This recombinant erythropoietin, a 165-amino acid glycoprotein (about 62% protein and 38% carbohydrate), regulates red blood cell production. Epoetin alfa is produced by Chinese hamster ovary cells into which the human erythropoietin gene has been inserted. (USP Dictionary of USAN and International Drug Names, 1996).
These growth factors comprise a family of hematopoietic regulators with biological specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. ERYTHROPOIETIN and the COLONY-STIMULATING FACTORS belong to this family. Some of these factors have been studied and used in the treatment of chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...