Patients with Refractory Chronic Myelogenous Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic. MedDRA version: 9.1 Level: LLT Classification code 10009013 Term: Chronic myeloid leukaemia
Conditions
Interventions
Product Code: MK0457
Pharmaceutical Form: Solution for infusion
Current Sponsor code: MK0457
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Trade Name: dasati
Sponsors
MERCK SHARP DOHME
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Patients must have chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). 2 Patients must be at least 3 months from the start of dasatinib therapy and are currently receiving dasatinib therapy for CML or Ph+ ALL and be evaluable for hematologic response prior to entering the study. 3 Patient is able to be treated with a 70 mg bid dose of dasatinib without significant toxicity at the time of study entry. 4 Patient is male or female of any race, and ≥18 years of age on day of signing informed consent. 1 Patient must have performance status ≤ 2 on the ECOG Performance Scale (Appendix 6.1). 6. Patients must have the following laboratory values unless considered due to leukemia: i) ALT and AST ≤ 2.5 x upper limit of normal (ULN) ii) Serum total bilirubin ≤ 2.0 x ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 2.0 ULN iii) Serum creatinine ≤ 1.5 x ULN OR ≥ 60ml/min for patients with creatinine levels >1.5 X institutional ULN 2 Female patient of childbearing potential has a negative serum or urine pregnancy test within 14 days of study enrollment. 3 Patient, or the patient?s legal representative, has voluntarily agreed to participate by giving written informed consent. 4 Patients with active CNS disease are included and may be treated concurrently with intrathecal therapy as per institutional standards. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1 Patient has had treatment with any anti-leukemia therapy (investigational or approved) other than dasatinib during the preceding 3 months. Pheresis or hydroxyurea treatment in the preceding 3 months will not exclude patients from eligibility. 2 Patient has unresolved ≥ grade 2 clinically significant toxicity attributed to dasatinib at the time of study entry. 3 Patient has known hypersensitivity to the components of study drug or its analogs. 4 Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient?s participation for the full duration of the study, or is not in the best interest of the patient to participate. 5 Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 1 Patient is, at the time of signing informed consent, a regular user (including ?recreational use?) of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse. 2 Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study. 3 Patient has symptomatic ascites, pericardial or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible. 4 Patient has had prior radiation therapy to more than 10% of the bone marrow; patients must have recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy. 5 Patient has a LVEF <40% by multigated radionucleotide angiography (MUGA) or echocardiography.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary (1) To determine dose-limiting toxicities (DLT), the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of MK-0457 administered in combination with dasatinib in patients with treatment-refractory CML or Ph+ ALL. Hypothesis: Administration of MK-0457 in combination with dasatinib will be sufficiently safe and tolerated to permit further study in CML and Ph+ ALL. (2) To determine pharmacokinetics of MK-0457 given in combination with dasatinib.;Secondary Objective: Secondary To evaluate the efficacy of MK-0457 in combination with dasatinib as measured by the induction or durability of hematologic response, cytogenetic response, or molecular response. Hypothesis: MK-0457 administered in combination with dasatinib will either induce response in patients not responding to dasatinib after 3 months of dasatinib monotherapy, or will prolong the duration of response in patients responding to dasatinib after 3 months of dasatinib monotherapy. 2.1.3 Exploratory To assess the pharmacodynamics (inhibition of Aurora kinases and BCR-ABL) of MK¬0457 in combination with dasatinib in patients with treatment-refractory CML or Ph+ ALL.;Primary end point(s): Primary (1) To determine dose-limiting toxicities (DLT), the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of MK-0457 administered in combination with dasatinib in patients with treatment-refractory CML or Ph+ ALL. Hypothesis: Administration of MK-0457 in combination with dasatinib will be sufficiently safe and tolerated to permit further study in CML and Ph+ ALL. (2) To determine pharmacokinetics of MK-0457 given in combination with dasatinib. Hypothesis: Administration of dasatinib with MK-0457 will not significantly alter the pharmacokinetics of MK-0457. | — |
Countries
Italy
Outcome results
None listed