Clinical trial NCT00316953 (phase 1, status: completed)
Conditions: accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic myelogenous leukemia, bcr-abl1 positive, meningeal chronic myelogenous leukemia, recurrent childhood acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, unspecified childhood solid tumor, protocol specific
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, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53, M94.1, A68.9, A68.0, A68.1, M35.6, H01.009, H02.209, H02.009, H02.109, H04.209, H05.409, H10.509
Drugs: dasatinib
SMILES: CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of 1 of the following:

               -  Malignant extracranial solid tumor

                    -  Recurrent or refractory disease

                    -  Known bone marrow metastases* allowed

               -  Imatinib mesylate-resistant Philadelphia chromosome-positive (Ph+) acute
                  lymphoblastic leukemia (ALL), defined as M3 bone marrow in a patient who
                  previously received imatinib mesylate-containing treatment regimen

               -  Imatinib mesylate-resistant Ph+ chronic myelogenous leukemia (CML), as defined by
                  any of the following:

                    -  Increasing WBC or platelet count while on imatinib mesylate therapy

                    -  Lack of any cytogenetic response after an adequate duration of imatinib
                       mesylate therapy, as defined by 1 of the following:

                         -  Failed to achieve a complete hematologic response after completion of 3
                            months of imatinib mesylate treatment

                         -  Failed to achieve a partial or complete cytogenetic response (i.e., ≤
                            35% Ph+ cells) after 6 months of imatinib mesylate treatment

                    -  Appearance of accelerated or blastic feature while on imatinib mesylate
                       therapy

                    -  Reappearance of Ph+ clones after an initial complete cytogenetic response to
                       imatinib mesylate

                    -  More than 30% increase in Ph+ cells in peripheral blood or bone marrow
                       cytogenetics while on imatinib mesylate therapy

                    -  Imatinib mesylate intolerance, as defined by development of adverse effects
                       requiring discontinuation of imatinib mesylate therapy

          -  Measurable disease (for patients with CML or ALL)

               -  Determined by hematologic, cytogenetic, and molecular studies for CML

               -  Determined by bone marrow blast percentage for ALL

          -  Measurable or evaluable disease (for patients with solid tumors)

          -  No known curative therapy or survival-prolonging therapy with an acceptable quality of
             life

          -  No CNS solid tumors

               -  CNS-positive leukemia allowed

          -  Karnofsky performance status (PS) ≥ 50% (for patients > 10 years of age)

          -  Lansky PS ≥ 50% (for patients ≤ 10 years of age)

          -  No evidence of graft-vs-host disease

          -  Solid tumors:

               -  Absolute neutrophil count ≥ 1,000/mm^3 (750/mm^3 if bone marrow infiltration)

               -  Platelet count ≥ 100,000/mm^3 (transfusion independent) (50,000/mm^3 if bone
                  marrow infiltration)

               -  Hemoglobin ≥ 8.0 g/dL (red blood cell [RBC] transfusions allowed)

          -  ALL/CML:

               -  Platelet count ≥ 20,000/mm^3 (platelet transfusions allowed)

               -  Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)

          -  Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
             creatinine based on age, as follows:

               -  No greater than 0.6 mg/dL (1-23 months of age)

               -  No greater than 0.8 mg/dL (2- 5 years of age)

               -  No greater than 1.0 mg/dL (6-9 years of age)

               -  No greater than 1.2 mg/dL (10-12 years of age)

               -  No greater than 1.4 mg/dL (13 years of age and over [female])

               -  No greater than 1.5 mg/dL (13-15 years of age [male])

               -  No greater than 1.7 mg/dL (16 years of age and over [male])

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  ALT ≤ 110 U/L

          -  Albumin ≥ 2 g/dL

          -  Normal 12-lead EKG with corrected QTc < 450 msec AND meets 1 of the following
             criteria:

               -  Shortening fraction normal

               -  Ejection fraction normal

          -  No evidence of dyspnea at rest

          -  No exercise intolerance

          -  Pulse oximetry > 94% if there is a clinical indication for determination

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No uncontrolled infection

          -  No swallowing dysfunction that would prevent taking an oral or liquid medication

          -  See Disease Characteristics

          -  Recovered from prior chemotherapy, immunotherapy, or radiotherapy

          -  No myelosuppressive chemotherapy within the past 3 weeks (6 weeks for nitrosoureas)

          -  At least 7 days since prior growth factors

          -  At least 14 days since prior pegfilgrastim

          -  At least 7 days since prior biologic agents

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

          -  At least 3 months since prior total-body irradiation, craniospinal radiation, or
             radiation to ≥ 50% of the pelvis

          -  At least 6 weeks since other prior substantial bone marrow radiation

          -  At least 3 months since prior stem cell transplantation

          -  Hydroxyurea cytoreduction for Ph+ leukemia allowed provided it is discontinued 24
             hours before first dose of dasatinib

          -  Prior intrathecal (IT) therapy allowed (for patients with CNS-positive leukemia)

          -  Concurrent IT therapy comprising hydrocortisone, cytarabine, methotrexate, or
             cytarabine (liposomal) allowed (for patients with CNS-positive leukemia)

          -  No other concurrent investigational drugs

          -  No other concurrent anticancer agents, including chemotherapy, radiotherapy,
             immunotherapy, or biologic therapy

          -  No concurrent enzyme-inducing anticonvulsants, including any of the following:

               -  Phenytoin

               -  Phenobarbital

               -  Carbamazepine

               -  Felbamate

               -  Primdone

               -  Oxcarbazepine

          -  No concurrent antithrombotic or antiplatelet agents, including any of the following:

               -  Warfarin

               -  Heparin

               -  Low-molecular weight heparin

               -  Aspirin

               -  Ibuprofen

               -  Other nonsteroidal anti-inflammatory drugs

          -  No concurrent CYP3A4 inhibitors, including itraconazole, ketoconazole, and
             voriconazole

          -  No concurrent highly active antiretroviral treatment for HIV-positive patients