Randomized Phase II Trial of timed Sequential Therapy (TST) with Alvocidib (Flavopiridol), ara-C and mitoxantrone (FLAM) vs. "7+3" for Adults age 70 and Under with Newly Diagnosed Acute Myelogenous Leukemia (AML)
B Douglas Smith
The purpose of this research study is to compare two different chemotherapy regimens to try to find out which way might be safer and/or more effective against AML. This is a Phase II study. Phase II studies are designed to examine whether specific drugs or drug combinations have activity against a specific type of cancer. The combination of flavopiridol with ara-C and mitoxantrone (FLAM) is an experimental combination for treating newly diagnosed AML with high risk features. In this study the flavopiridol, ara-C and mitoxantrone is being compared to traditional chemotherapy used to treat newly diagnosed AML of ara-C and daunorubicin (7+3).
Tumor Types: All Adults age greater than 18 years and less than 70 years with Newly Diagnosed, Intermediate Risk or Poor-Risk AML. Performance Status: ECOG Performance Status 0-3, patients greater than 65 years of age must have ECOG performance status less than 2 prior to developing leukemic symptoms. Organ Function ï¿½ Low blood cell counts (ie, platelets, RBC's, WBC's)are allowed ï¿½ Normal kidney and liver function required ï¿½ Normal heart function required Allowed Prior Therapy: Hydroxyurea, non-cytotoxic therapy for MDS or MPN (e.g., thalidomide or lenidomide, interferon, cytokines, 5-azacytidine or decitabine, histone deacetylase inhibitors, low-dose cytoxan, tyrosine kinase or dual TK/src inhibitors) will be eligible for this trial. Exclusion Criteria: Patients cannot have been treated previously with flavopiridol. Patients cannot be diagnosed with core-binding factor AML's. Patients cannot have APL, greater than 50,000blasts/uL, simultaneous treatment with other chemotherapy, radiation, or immunotherapy, uncontrolled infection, active CNS leukemia, active GVHD, or other life threatening illnesses. The patient cannot be pregnant or nursing.
To diagnose your disease we will perform a bone marrow aspirate and/or biopsy. A bone marrow aspiration is a procedure in which an area of the hip is numbed and a small sample of bone marrow is withdrawn. A bone marrow biopsy is similar to a bone marrow aspiration except a sample of bone is removed through the needle. To see if you are eligible to take part in this study, a medical history will be taken, a physical exam will be done, and all of your current medications will be reviewed. If you take part in this study, you will complete the following as part of the research study. You will be randomly assigned (by chance, like the flip of a coin) to one of two chemotherapy regimens. The study plan is as follows, with the first day of therapy being â??Day 1:â?? Arm A (FLAM): â?¢ Flavopiridol will be administered daily for 3 days by 60 minute intravenous (IV) beginning Day 1 â?¢ Cytosine Arabinoside (ara-C) will be administered by continuous IV infusion for 72 hours beginning on Day 6 â?¢ Mitoxantrone will be administered by IV infusion over 60-120 minutes on Day 9, 12 hours after completion of ara-C infusion Arm B (7+3): â?¢ Daunorubicin will be administered IV over 30-60 minutes Days 1, 2, 3 â?¢ Cytosine arabinoside (ara-C) will be administered by continuous IV infusion for a total of 7 days beginning Day 1 The average length of this cycle is 4 to 6 weeks or until you finish the first cycle of study drugs. Typically, a 3-4 week hospitalization is expected with each cycle. Even when you have completed the study, we will continue to follow you indefinitely to monitor your leukemia and your survival. This may be done by clinic visits to your doctor, by obtaining notes and lab reports from your local doctor, and/or telephone or email contact with yourself. This contact will occur every 3 months for at least 2 years, then every 6 month until 5 years from treatment, then annually.
05/22/2013 04:02 AM