A Phase II Study of MK-0457 in Patients With BCR-ABL T315I Mutant Chronic Myelogenous Leukemia and Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia - ND

• Conditions: cronic myeloid leukemia with mutation BCR-ABL T3151 and acule linfopblastic leukemia PH+; MedDRA version: 6.1Level: HLTClassification code 10024291

• Registration Number: EUCTR2006-004535-30-IT
• Lead Sponsor: MERCK SHARP DOHME

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-05-15
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 272

Inclusion Criteria

Patient is male or female, and >=18 years of age on day of signing informed consent. 2. ECOG performance status: a) For Accelerated Phase CML, Blastic phase CML, and Ph+-ALL patients: ECOG <=3 b) For Chronic Phase CML patients: ECOG <= 2 3. The interval from prior treatment (standard or investigational) to time of study drug administration should be at least 2 weeks for cytotoxic agents or at least 5 half-lives for non-cytotoxic agents. The only exception is hydroxyurea which can be used to control peripheral leukemic cell counts prior to initiating study drug and during the first treatment cycle. Persistent clinically significant chronic toxicities from prior chemotherapy must not be greater than Grade 2 (except alopecia). 4. Patients must have the following laboratory values unless considered due to leukemia: a) ALT and AST <= 3 x upper limit of normal (ULN) b) Serum total bilirubin <= 1.5 x ULN (except for known Gilbert?s syndrome) c) Serum creatinine <= 2.0 x ULN 5. Patient, or patient?s legal representative, has voluntarily agreed to participate by giving informed consent. 6. Patients with active CNS disease may be included and will be treated concurrently with intrathecal therapy.Patients under consideration for inclusion into this study must have Ph+ (or BCRABL+) CML or ALL and meet one of the following disease inclusion criteria: a) Patients diagnosed with CML in blastic phase. Any number of prior therapies is permitted. Patients are considered to have CML in blastic phase if they meet either of the following criteria: (1) At least 30% blasts in the peripheral blood or bone marrow or extramedullary disease other than spleen. b) Patients diagnosed with accelerated phase CML. Any number of prior therapies is permitted. Patients are considered to have CML in accelerated phase if they do not qualify as blastic phase and meet at least one of the following criteria: (1) At least 15% to < 30% blasts in peripheral blood or 15% to < 30% blasts in bone marrow. (2) The sum of the percent blasts plus percent promyelocytes in peripheral blood or in the bone marrow is at least 30% (but the percent blasts alone is < 30%). (3) Peripheral basophils > 20%. (4) Thrombocytopenia <100 x 109/L unrelated to therapy. c) Patients diagnosed with chronic phase CML and further therapy is clinically indicated. Chronic phase CML patients must have failed at least imatinib therapy to be eligible. Patients are considered to have CML in chronic phase, defined as never in accelerated phase or blastic phase, if they meet the following criteria: (1) <15% blasts in the peripheral blood and bone marrow. (2) <30% blasts plus promyelocytes in peripheral blood and bone marrow. (3) <20% basophils in the peripheral blood. (4) >=100 x 109/L platelets. (5) No evidence of extramedullary leukemic involvement, with the exception of the liver or spleen. d) Patients diagnosed with Ph+-ALL. Any number of prior therapies is permitted. Patients with Ph+-ALL are also eligible if they have one of the following criteria:Patients with minimal residual disease (MRD) are eligible only if there is indication of evolving relapse defined as a >= 2 log increase of BCR-ABL transcript level (as reported by local laboratories), as compared to the minimum level achieved with prior therapies in the peripheral blood or bone marrow [8]. (2) Patients with Ph+-ALL whose disease exhibits features of biphenotypic acute leukemia are eligible [9].

Exclusion Criteria

Patient has not fully recovered from acute side effects of prior anti-leukemic therapy to <= Grade 2 toxicity, except alopecia. 2. Patient within 3 months of allogeneic bone marrow transplant and/or has active and uncontrolled Graft-versus-Host disease following allogeneic bone marrow transplant and/or not on a stable dose of immunosuppressants for at least one month. 3. Patient has uncontrolled symptomatic congestive heart failure, angina, or had a myocardial infarction in the preceding 3 months. 4. Patient has known hypersensitivity to the components of study drug or its analogs. 5. Patient has uncontrolled active infection. 6. Patient has a known psychiatric or substance abuse disorder that in the opinion of the Investigator would interfere with cooperation with the requirements of the trial. 7. Patient is pregnant or breastfeeding or expecting to conceive within the projected duration of the study.Patient has any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 9. Patients with ?currently active? second malignancy, other than non-melanoma skin cancer, should not be enrolled. Patients are not considered to have a ?currently active? malignancy if they have completed therapy for a prior malignancy and are considered by their treating physician to be at less than 30% risk of relapse. 10. Patient is known to be HIV seropositive or who has an AIDS-related illness. 11. Patient has known active hepatitis B or C (and/or treated previously with abnormal liver function tests). 12. Patient has a LVEF >40% by multigated radionucleotide angiography (MUGA) or echocardiography.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of MK-0457, as defined by major cytogenetic response in chronic phase CML and as major hematological response in accelerated phase CML, blastic phase CML, and Ph+-ALL, when given as a 5-day CIV infusion every 14 days.;Secondary Objective: To evaluate the durability of responses with MK-0457.;Primary end point(s): The primary<br><br>endpoint will be major cytogenetic response for chronic phase (CP) CML, and major<br><br>hematological responses, which include complete and no evidence of leukemia (NEL)<br><br>hematological responses for accelerated phase (AP) and blastic phase (BP) CML, and<br><br>Ph+-ALL. Patients who have a suitable bone marrow donor can go off study for bone<br><br>marrow transplant as curative therapy. Hematologic, cytogenetic, and molecular<br><br>responses will be evaluated from peripheral blood, bone marrow, and lumbar puncture<br><br>(when applicable) throughout the study.