A Phase I Dose Escalation Combination Study in Patients With Chronic Myelogenous Leukemia (CML) and Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL)(0457-009)(TERMINATED)

A Phase I Dose Escalation of MK0457 in Combination With Dasatinib in Patients With Chronic Myelogenous Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

This study will evaluate MK0457 in combination with Dasatinib in patients with Chronic Myelogenous Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Efficacy and Safety will be evaluated.

Study Overview

• Status: Terminated
• Conditions: Chronic Myelogenous Leukemia; Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
• Intervention / Treatment: Drug: MK0457; Drug: dasatinib

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
• 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
• Patient is able to be treated with a 70 mg bid dose of dasatinib without significant toxicity at the time of study entry
• Patients with active CNS disease are included and may be treated concurrently with intrathecal therapy as per institutional standards

Exclusion Criteria:

• 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
• Patient has unresolved more than or equal to grade 2 clinically significant toxicity attributed to dasatinib at the time of study entry
• Patient has known hypersensitivity to the components of study drug or its analogs
• Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study
• Patient has symptomatic ascites, pericardial or pleural effusion. A patient who is clinically stable following treatment for these conditions is eligible
• 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
• Patient has a LVEF <40% by multigated radionucleotide angiography (MUGA) or echocardiography

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: A; Arm A: Drug and comparator	Drug: MK0457; Schedule A: 5-day continuous IV infusion every 28 days MK0457 (dose determined by height and weight). Starting dose = 20 mg/m2/hour titrating up to 33 mg/m2/hour. Schedule B: 6-hr IV infusion every 14 days MK0457 (dose determined by height and weight). Starting dose = 64 mg/m2/hour titrating up to 216 mg/m2/hour.; Drug: dasatinib; Oral dasatinib 70 mg b.i.d. tablets twice daily.; Other Names: Sprycel®
Other: B; Arm B: Drug and comparator	Drug: MK0457; Schedule A: 5-day continuous IV infusion every 28 days MK0457 (dose determined by height and weight). Starting dose = 20 mg/m2/hour titrating up to 33 mg/m2/hour. Schedule B: 6-hr IV infusion every 14 days MK0457 (dose determined by height and weight). Starting dose = 64 mg/m2/hour titrating up to 216 mg/m2/hour.; Drug: dasatinib; Oral dasatinib 70 mg b.i.d. tablets twice daily.; Other Names: Sprycel®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics, Safety, Tolerability	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamics, Hematologic Response, Cytogenetic Response, Molecular Response, Response Durability	28 Days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Okabe S, Tauchi T, Ohyashiki K. Efficacy of MK-0457 and in combination with vorinostat against Philadelphia chromosome positive acute lymphoblastic leukemia cells. Ann Hematol. 2010 Nov;89(11):1081-7. doi: 10.1007/s00277-010-0998-x. Epub 2010 Jun 20.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: July 10, 2007
• First Submitted That Met QC Criteria: July 11, 2007
• First Posted (Estimate): July 12, 2007

Study Record Updates

• Last Update Posted (Estimate): January 30, 2015
• Last Update Submitted That Met QC Criteria: January 29, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia, Lymphoid; Chromosome Aberrations; Translocation, Genetic; Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: 0457-009; 2007_509