Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Preleukemia

Myelodysplastic Syndromes

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Leukemia, Myelomonocytic, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Leukemia, Myeloid

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Azacitidine

Epoetin Alfa

Antimetabolites

Enzyme Inhibitors

100 mg / m(2) subcutaneously day 1-5 every 4 weeks for 6 cycles. Another three cycles will be given together with epo for those not responding to the first 6 cycles of Azacitidine

For those patients not responding to Azacitidine alone, the combination of Azacitidine and erythropoetin 60 000 U / week for 16 weeks will be given.

Erythropoetin

Magnus Tobiasson, M.D.

Azacitidine has proved prolonged overall survival in patients with high-risk MDS. Minor pilot studies have shown that treatment with Azacitidine can induce transfusion independency in previous transfusion dependent patients with low-risk MDS. This study will evaluate the effect of Azacitidine in transfusion dependent patients with low-risk MDS (IPSS low or int-1) or low risk CMML. Included patients should first have failed, or considered not being eligible to, treatment with EPO +/- G-CSF. Our hypothesis is that Azacitidine can lead to transfusion independency in this group of patients. Those patients who do not respond to treatment with Azacitidine alone, will be given treatment with the combination of Azacitidine and EPO where our hypothesis is that Azacitidine can restore sensitivity to EPO.

Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

Clinical and Biological Evaluation of Azacitidine in Transfusion-dependent Patients With Low and Intermediate-1 Risk MDS, and Low-risk CMML, Who Are Either Refractory to or Not Eligible for Treatment With Erythropoietin +/- G-CSF

Nordic MDS Group

Leukemia, Myeloid, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Xavier THOMAS, MD-PhD

Acute myeloid leukaemia (AML) is a haematological malignant disease characterized by an uncontrolled proliferation of immature hematopoietic cells. Over the last two decades, clinical trials have demonstrated an improved response rate in younger adult AML. Aggressive induction plus more potent intensification programs with chemotherapy alone or chemotherapy plus stem cell transplantation (SCT) has improved treatment results. Advances in understanding disease biology, improvements in induction and consolidation program, and better supportive care have also all contributed. A number of clinical and laboratory characteristics influence the response to treatment and, thus, the survival of patients with AML. Among them, cytogenetic at diagnosis represents the most important prognostic variable. However, other factors may have a prognostic value and may influence patient's outcome.

Anaemia and thrombocytopenia are cardinal manifestations of AML. Over the last decades, it has become apparent that the frequency of allogeneic blood transfusions can modify host immunity and clinical outcomes. Anaemia has long been recognized as an adverse prognostic factor in myelodysplastic syndrome (MDS), which represents a pre-leukemic disease. Red blood cell (RBC) transfusion need was identified as a strong and independent risk factor for survival in MDS, for which the presence and severity of anaemia were attributed to a clonally advanced and biologically more aggressive disease.

Based on these data, the investigators retrospectively assessed the prognostic value of RBC and platelet transfusions at the time of diagnosis and the frequency of transfusions during the first induction course of chemotherapy in a large unselected group of patients with previously untreated AML.

Transfusion Dependency at Diagnosis and Transfusion Intensity During Initial Chemotherapy Are Associated With Poorer Outcomes in Adult Acute Myeloid Leukaemia

Overall survival (OS) is defined as the time elapsed between induction chemotherapy regimen and death for any cause. Patients not known to have this event are censored on the date they were last examined

Response to induction therapy was assessed after one or two courses of chemotherapy (Between day 28 and day 35 of each course of chemotherapy). CR was defined according to standard criteria as less than 5 % blasts in bone marrow aspirates with evidence of maturation of cell lines and restoration of peripheral blood counts.

Transfusion of a single unit of packed red blood cell (PRBC) or one whole-blood-derived platelet concentrate (PC) or platelets collected by apheresis (PA).

Prophylactic transfusions were consistently given at morning platelet counts of \<20×109/l and haemoglobin level \<80 g/l. Patients requiring platelets were transfused with PC (PCs pooled from several units with 0.7 to 1×1011 platelets/10 kg of weight). Blood products were leukoreduced through discarding the buffy coat and administered through a standard blood filter but were not irradiated or routinely leukodepleted. Only patients planned to be allografted or autografted were transfused with irradiated transfusion products.

Hospices Civils de Lyon

Acute myeloid leukaemia (AML) is a haematological malignant disease characterized by an uncontrolled proliferation of immature hematopoietic cells. Over the last two decades, clinical trials have demonstrated an improved response rate in younger adult AML. Aggressive induction plus more potent intensification programs with chemotherapy alone or chemotherapy plus stem cell transplantation (SCT) has improved treatment results. Advances in understanding disease biology, improvements in induction and consolidation program, and better supportive care have also all contributed. A number of clinical and laboratory characteristics influence the response to treatment and, thus, the survival of patients with AML. Among them, cytogenetic at diagnosis represents the most important prognostic variable. However, other factors may have a prognostic value and may influence patient's outcome.

Anaemia and thrombocytopenia are cardinal manifestations of AML. Over the last decades, it has become apparent that the frequency of allogeneic blood transfusions can modify host immunity and clinical outcomes. Anaemia has long been recognized as an adverse prognostic factor in myelodysplastic syndrome (MDS), which represents a pre-leukemic disease. Red blood cell (RBC) transfusion need was identified as a strong and independent risk factor for survival in MDS, for which the presence and severity of anaemia were attributed to a clonally advanced and biologically more aggressive disease.

Based on these data, we retrospectively assessed the prognostic value of RBC and platelet transfusions at the time of diagnosis and the frequency of transfusions during the first induction course of chemotherapy in a large unselected group of patients with previously untreated AML.

Transfusion in Adult Acute Myeloid Leukemia

Transfusion Dependency at Diagnosis and Transfusion Intensity During Initial Chemotherapy Are Associated With Poorer Outcomes in Adult Acute Myeloid Leukemia

Response to induction therapy was assessed after one or two courses of chemotherapy. CR was defined according to standard criteria as less than 5 % blasts in bone marrow aspirates with evidence of maturation of cell lines and restoration of peripheral blood counts

Thrombocytopenia

Blood Platelet Disorders

Cytopenia

In this study 4 different doses of oral eltrombopag (50mg, 100mg, 200mg and 300mg) will be tested. A modified 3+3 patient cohorts design will be used so no new patients are accepted to start on a higher dose without prior tolerance at the previous dose. Patients will be given eltrombopag once daily starting one week before the start of azacitidine treatment and then continue throughout the study, which duration will be approximately 3 months (three Azacytidine cycles). Patients will be evaluated continuously by clinical and laboratory assessments as well as bone marrow examinations during the treatment period until 4 weeks after discontinuation of Eltrombopag. Response, AEs/SAEs and DLTs will be monitored throughout the study.

Eltrombopag

Tobias Svensson, M.D.

Patients with Myelodysplastic Syndromes (MDS) often suffer from low platelet levels which may lead to bleeding complications. Treatment with cytotoxic agents can decrease the platelet levels further. Eltrombopag is a relatively new drug that increases the platelet level in the blood by working directly on the bone marrow. It is available for treatment of the disease Immunological Thrombocytopenic Purpura (ITP). In this study patients with MDS and low platelet levels that are treated with the cytotoxic agent Azacitidine will also receive Eltrombopag. The administration of Eltrombopag to MDS patients treated with Azacitidine may result in less dose reductions and less treatment delays for Azacitidine and may reduce the need for thrombocyte transfusions and lower the risk of bleeding complications.

This is a phase I study, meaning that our major goal is to investigate the safety and tolerability for Eltrombopag in this patient group. It will also generate a basis for a phase II-III-study.

Safety Study of Eltrombopag Combined With Azacitidine to Treat Myelodysplastic Syndrome (MDS)

A Pilot Phase I Dose Finding Safety Study of a Thrombopoietin-receptor Agonist, Eltrombopag, in Patients With Myelodysplastic Syndrome Treated With Azacitidine

Including:

* Non-hematological clinical, laboratory Grade 3/Grade 4 toxicities
* Change in bone marrow or peripheral blood blast counts from baseline
* Adverse events and interactions at increasing doses of eltrombopag

GlaxoSmithKline

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)	NCT01048034	Myelodysplastic... Chronic Myelomo...	Azacitidine Erythropoetin	18 Years -	Nordic MDS Group
Transfusion Dependency at Diagnosis and Transfusion Intensity During Initial Chemotherapy Are Associated With Poorer Outcomes in Adult Acute Myeloid Leukaemia	NCT02844257	Acute Myeloid L...		15 Years - 83 Years	Hospices Civils de Lyon
Transfusion in Adult Acute Myeloid Leukemia	NCT02899767	Acute Myeloid L...		15 Years -	Hospices Civils de Lyon
Transfusion in Adult Acute Myeloid Leukemia	NCT02899767	Acute Myeloid L...		15 Years -	Hospices Civils de Lyon
Transfusion in Adult Acute Myeloid Leukemia	NCT02899767	Acute Myeloid L...		15 Years -	Hospices Civils de Lyon
Safety Study of Eltrombopag Combined With Azacitidine to Treat Myelodysplastic Syndrome (MDS)	NCT01481220	Myelodysplastic... Thrombocytopeni...	Eltrombopag	18 Years -	Nordic MDS Group
Transfusion Dependency at Diagnosis and Transfusion Intensity During Initial Chemotherapy Are Associated With Poorer Outcomes in Adult Acute Myeloid Leukaemia	NCT02844257	Acute Myeloid L...		15 Years - 83 Years	Hospices Civils de Lyon

Spots Global Cancer Trial Database for transfusion dependency