A Phase I Study of Pomalidomide Given at the Time of Lymphocyte Recovery Following Induction Timed Sequential Chemotherapy with Cytarabine, Daunorubicin and Etoposide (AcDVP16) in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) and High-Risk MDS
The purpose of this study is to test the safety of a study drug called pomalidomide when it is given by mouth after standard chemotherapy. This study tests different doses of the drug to see which dose is safe. Pomalidomide is similar to the drug thalidomide or lenalidomide. This study is being done to find the highest dose of pomalidomide that can safely be given by mouth after chemotherapy. We additionally are looking to determine if pomalidomide can assist the immune system to keep leukemia from recurring. Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. It is the most common type of acute leukemia in adults. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocyticleukemia, and acute nonlymphocytic leukemia.The 2 treatment phases of adult AML are:ï?· Remission induction therapy: This is the first phase of treatment. The goal is to kill the leukemia cells in the blood and bone marrow. This puts the leukemia into remission.ï?· Post-remission therapy: This is the second phase of treatment. It begins after the leukemia is in remission. The goal of post-remission therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse. This phase is also called remission continuation therapy.
Tumor Types: Adults 18 years through 65 years with newly diagnosed acute myeloid leukemia (AML) subtypes M0,1,2,4-7 but excluding newly diagnosed core-binding factor (CBF) AMLs and acute promyelocytic leukemia (APL, M3). Performance Status: ECOG 0-2Abnormal Organ Function Permitted: ï¿½ Multilineage Bone Marrow Failureï¿½ Bilirubin less than 2 mg/dL unless due to Gilbertï¿½s Disease, hemolysis, or leukemic infiltrationï¿½ AST(SGOT)/ALT(SGPT) less than 5x upper limit normal ï¿½ Serum Creatinine less than 2 mg/dLï¿½ Left Ventricular Ejection Fraction greater than 45%Prior Therapy: ï¿½ Prior Hydroxyurea permitted for cytoreductionï¿½ greater than 2 weeks off non-cytotoxic therapies permitted (e.g. azacitidine, decitabine, histone deacetylase inhibitors, tyrosine kinase inhibitors, hematopoietic growth factors, interferon)ï¿½ greater than 3 months off Immunomodulatory drugs (e.g. lenalidomide, thalidomide) ï¿½ Cyclophosphamide for cytoreduction
Acute myeloid leukemia (AML) is a heterogeneous disease both biologically and clinically. Despite the therapeutic progress made over the last 30 years, treatment outcomes remain suboptimal. Only one third of younger patients with AML are ultimately cured and older patients, which comprise the majority of those with AML, achieve long-term survival less than 10% of the time. A number of factors are known to affect the success of chemotherapy. Adults with poor-risk features at diagnosis have an extremely poor prognosis in terms of achievement and duration of a complete remission (CR). Poor risk features in AML include secondary AML (ie. treatment-related or arising from an antecedent hematologic disorder), AML with adverse cytogenetics (including chromosome 3 abnormalities, -5/5q, -7/7q, +8, 11q23 abnormalities, 20q-, complex karyotypes) and adverse genetics (such as FLT3 mutations). For such patients, CR is achieved in less than 50% with long term survival in less than 10%, while the CR rate for patients without poor-risk features is greater than 70% with intensive cytotoxic chemotherapy consisting of cytarabine and an anthracycline + etoposide and long term survival still only 30-40%. CR rate and duration also decrease with increasing age (i.e., age greater than 60), with CR rates consistently less than 40%, even in the absence of overt poor-risk disease, and a 3-5 year survival less than 10-15%. Thus, while the CR rate for conventional therapy in newly diagnosed AML approaches 70%, relapse remains the major reason for therapeutic failure. The overall outcome for patients who relapse is dismal, with median overall survival (OS) less than 1 year, and long-term survival less than 10%. Thus, there is an urgent need for more effective upfront therapy to prevent or delay relapse. This trial is supported by CTEP and the UO-1 grant.
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