Clofarabine Combinations in Relapsed/Refractory Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS) and Myeloid Blast Phase Chronic Myeloid Leukemia (CML)
Condition: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The goal is to compare the drug combinations clofarabine/idarubicin/ara-C, clofarabine/ara-C,
      and clofarabine/idarubicin in the treatment of patients with Acute Myeloid Leukemia,
      high-grade MDS, or myeloid blast phase of Chronic Myeloid Leukemia who have relapsed
      following their initial therapy.
    

Detailed description: 
      Clofarabine is a new drug that was designed to help treat leukemia. Ara-C and idarubicin are
      drugs that are commonly used to help treat leukemia.

      Before treatment starts, you will be asked questions about your medical history and have a
      complete physical exam. You will have blood samples (about 1 tablespoon) collected for
      routine lab tests. You will either have an echocardiogram or a multiple-gated acquisition
      (MUGA) scan to check on the function of your heart. You will have a sample of bone marrow
      collected to check on the status of the disease. To collect a bone marrow sample, an area of
      the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is
      withdrawn through a large needle. Women who are able to have children must have a negative
      blood or urine pregnancy test.

      After each cycle of therapy, you will not receive the next cycle of chemotherapy until your
      blood counts have recovered and any possible side effects have gone away (for around 3 to 6
      weeks). If the disease gets worse or side effects become too severe, treatment will stop. You
      must stay in Houston for the first 4 to 6 weeks (average) of treatment and are required to
      return to Houston to receive each additional cycle of chemotherapy (up to 6 days each cycle).

      You will be assigned to receive treatment with clofarabine plus idarubicin and ara-C.

      For participants in the clofarabine/idarubicin/ara-C group, the clofarabine will be given by
      vein over 1 hour once a day for 5 days in a row, on Days 2 to 6 of each cycle. Idarubicin
      will be given by vein over 30 minutes for 3 days in a row, on Days 1 to 3 of each cycle.
      Ara-C will be given by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
      Idarubicin is usually started around 1 hour after the completion of clofarabine, and ara-C
      about 4 hours after the start of the clofarabine infusion. This 6 day period is called a
      cycle of chemotherapy.

      You will receive at least 1 cycle of therapy. If after 1 or 2 cycles of therapy it is found
      that the disease is responding to therapy, you may continue to receive therapy for up to 4
      additional courses of "consolidation therapy". During the "consolidation therapy" you will
      also be given treatment courses with ara-C alone. When ara-C is given alone it will be given
      as a continuous infusion, 24 hours a day, for 5 days in a row. You will be given a portable
      pump so that this treatment can be done as an outpatient. The combination drug courses and
      the ara-C courses will alternate (ara-C alone, combination, ara-C alone, combination) for a
      total of 4 courses. If it is found that the disease is not responding to chemotherapy, you
      will be taken off the study and your doctor will discuss other treatment options with you.

      Before you receive each dose of drug(s), you will have a complete physical exam. During
      treatment, you will have blood (about 1 tablespoon) collected at least once a week during the
      first 2 courses of therapy, then every 2-4 weeks after. Bone marrow samples will be collected
      every other week during treatment to check on the status of the disease. The blood and bone
      marrow samples may be collected more often if your doctor feels it is necessary.

      If, at any time, the disease gets worse or you experience any intolerable side effects, you
      will be taken off the study and your doctor will discuss other treatment options with you.

      After your last course of treatment, you will have a follow-up visit scheduled. At this
      visit, you will have blood (about 1 tablespoon) collected for routine tests. You will have a
      sample of bone marrow collected to check on the status of the disease. You will also have a
      repeat echocardiogram or MUGA scan to check on the function of your heart.

      This is an investigational study. Clofarabine has been authorized by the FDA to be used in
      research only. Idarubicin and ara-C are both FDA approved and are commercially available. Up
      to 120 participants will take part in this study. All will be enrolled at M. D. Anderson.
    

Intervention name(s): Clofarabine 40mg/m^2; Idarubicin 10mg/m^2; Ara-C 0.75 g/m^2; Clofarabine 22.5mg/m^2; Ara-C 1 g/m^2; Idarubicin 6 mg/m^2
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 40 mg/m^2 by vein over 1 hour daily for 5 days.; 10 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Clofarabine + Idarubicin plus Ara-C:
6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.; 0.75 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.; 22.5 mg/m^2 by vein over 1 hour daily for 5 days.; 1 g/m^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.; 6 mg/m^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Other intervention name(s): Clofarex; Clolar; Idamycin®,; Idamycin PFS®; Cytosar-U®; Cytarabine; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride; Clofarex; Clolar; Cytosar-U®; Cytarabine; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride; Idamycin®,; Idamycin PFS®
Intervention MeSH terms: Cytarabine; Clofarabine; Idarubicin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic Myeloid Leukemia; CML Myeloid Blast Phase; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Clofarabine; Clofarex; Clolar; Ara-C; Cytarabine; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride; Idarubicin; Idamycin