Clinical trial NCT00030394 (phase 2, status: completed)
Conditions: childhood chronic myelogenous leukemia, chronic myelogenous leukemia, bcr-abl1 positive, chronic phase chronic myelogenous leukemia
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01
Drugs: imatinib mesylate
SMILES: CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)CC1
Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Philadelphia chromosome positive (Ph+) chronic phase chronic myelogenous
             leukemia (CML)

          -  Stratum I (closed to accrual as of 12/05/03):

               -  CML in first chronic phase with resistance to interferon alfa (IFN-A) therapy
                  defined as one of the following:

                    -  WBC count at least 20,000/mm^3 after at least 3 months of treatment with an
                       IFN-A-containing regimen

                    -  Rising WBC count (at least 100% increase to a level of at least 20,000/mm^3)
                       by two samples at least two weeks apart while receiving treatment with an
                       IFN-A-containing regimen

                    -  At least 66% Ph+ cells in bone marrow after 1 year of IFN-A therapy

                    -  At least 30% increase in Ph+ cells in bone marrow after IFN-A-induced
                       cytogenetic response while continuing to receive IFN-A therapy

               -  Intolerance to interferon therapy defined as more than two grade 2 toxic effects
                  or any grade 3 toxic effect related to interferon therapy, except grade 3 fever,
                  that is persistent beyond the first 28-day course of therapy and unresponsive to
                  standard supportive care interventions

          -  Stratum II (closed to accrual as of 7/29/05): CML recurring after stem cell
             transplantation or in second or subsequent chronic phase

               -  No molecular relapse (only evidence is detection of bcr-abl rearrangement with
                  normal bone marrow and blood morphology and normal standard cytogenetic analysis)

          -  Stratum III (closed to accrual as of 7/29/05): Newly diagnosed CML in first chronic
             phase with no prior treatment except hydroxyurea

          -  Stratum IV: Newly diagnosed CML in first chronic phase with no prior treatment except
             hydroxyurea

          -  No accelerated or blast phase defined as one or more of the following:

               -  WBC doubling time less than 5 days

               -  Chloroma

               -  Medullary fibrosis

               -  More than 10% blasts in peripheral blood or bone marrow

               -  More than 20% promyelocytes in peripheral blood or bone marrow

               -  More than 20% basophils and eosinophils in peripheral blood

          -  Performance status - ECOG 0-2

          -  At least 8 weeks

          -  See Disease Characteristics

          -  Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide
             angiogram

          -  Bilirubin no greater than 1.5 times normal

          -  ALT less than 3.0 times normal

          -  Albumin greater than 2 g/dL

          -  Creatinine no greater than 1.5 times normal

          -  Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No uncontrolled infection

          -  No CNS toxicity greater than grade 2

          -  See Disease Characteristics

          -  No prior immunotherapy (for patients in stratum III [closed to accrual as of 7/29/05]
             and stratum IV only)

          -  At least 3 months since prior stem cell transplantation (SCT) (patients with
             allogeneic SCT must have no active graft-versus-host disease [GVHD] and have stable
             use of steroids) (for patients in stratum II only )

          -  At least 1 week since prior growth factors

          -  At least 1 week since prior biologic therapy, including interferon alfa (for patients
             in stratum I [closed to accrual as of 12/05/03] and stratum II only)

          -  Recovered from prior immunotherapy

          -  No concurrent immunomodulating agents

          -  See Disease Characteristics

          -  No prior chemotherapy (for patients in stratum III [closed to accrual as of 7/29/05]
             and stratum IV only)

          -  At least 6 weeks since prior busulfan or nitrosoureas

          -  At least 7 days since prior hydroxyurea

          -  At least 7 days since prior low-dose cytarabine (less than 30 mg/m^2 every 12 to 24
             hours)

          -  At least 14 days since prior moderate-dose cytarabine (100-200 mg/m^2 for 5 to 7 days)

          -  At least 28 days since prior high-dose cytarabine (1-3 g/m^2 every 12 to 24 hours for
             6 to 12 doses)

          -  At least 21 days since all other cytotoxic chemotherapy

          -  Recovered from prior chemotherapy

          -  No concurrent chemotherapy

          -  No concurrent steroids other than for controlled GVHD in patients with prior
             allogeneic SCT

          -  No prior radiotherapy (for patients in stratum III [closed to accrual as of 7/29/05]
             and stratum IV only)

          -  At least 2 weeks since prior local palliative (small port) radiotherapy*

          -  At least 3 months since prior craniospinal radiotherapy or radiotherapy to 50% or more
             of pelvis*

          -  At least 6 weeks since prior substantial bone marrow radiotherapy*

          -  Recovered from prior radiotherapy

          -  No prior imatinib mesylate

          -  No concurrent enzyme-activating anticonvulsants

          -  No concurrent warfarin

          -  No concurrent naturopathic agents or herbal medicines

          -  No other concurrent investigational agents

          -  Concurrent low-molecular weight heparin allowed