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)

Chronic Myelogenous Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00500006
• Other study ID #: 0457-009
• Secondary ID: 2007_509
• Status: Terminated
• Phase: Phase 1
• First received: July 10, 2007
• Last updated: January 29, 2015
• Start date: October 2007
• Est. completion date: November 2007

Study information

• Verified date: January 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abnormal Karyotype
• Chronic Myelogenous Leukemia
• Leukemia
• Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.
• dasatinib
Oral dasatinib 70 mg b.i.d. tablets twice daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics, Safety, Tolerability		28 Days	Yes
Secondary	Pharmacodynamics, Hematologic Response, Cytogenetic Response, Molecular Response, Response Durability		28 Days	No