Effect of Imatinib Mesylate and the Pharmacokinetics of Acetaminophen/Paracetamol in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

A Non-randomized, Open-label Study to Investigate the Effects of Imatinib Mesylate on the Pharmacokinetics of Acetaminophen/Paracetamol in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

A non-randomized, open-label study to investigate the effects of imatinib mesylate on the pharmacokinetics of acetaminophen/paracetamol in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP)

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukemia (CML)
• Intervention / Treatment: Drug: Imatinib/Acetaminophen

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Ability to provide written informed consent prior to participation to the study.
• Male or female patients ≥ 18 and ≤ 75 years of age
• Patients with CML-CP within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis). FISH analysis will not be accepted.
• Diagnosis of CML in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations and presence of Bcr-Abl
• Documented chronic phase CML as defined by:
• < 15% blasts in peripheral blood and bone marrow
• < 30% blasts plus promyelocytes in peripheral blood and bone marrow
• < 20% basophils in the peripheral blood
• ≥ 100 x 109/L (≥ 100,000 /mm3) platelets
• No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
• Adequate end organ function as defined by:
• total bilirubin < 1.5 x ULN
• SGOT and SGPT < 2.5 x UNL
• creatinine < 1.5 x ULN
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before initiation of study drug

Exclusion criteria:

• Patients in late chronic phase, accelerated phase, or blastic phase are excluded
• Patients who have received other investigational agents
• Patients who received imatinib for any duration prior to study entry
• Patient received any treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide
• Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
• Patients who are:
• pregnant
• breast feeding
• of childbearing potential without a negative pregnancy test prior to baseline
• male or female of childbearing potential unwilling to use barrier contraceptive precautions throughout the trial
• Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
• Patient with a severe or uncontrolled medical condition (i.e., uncontrolled diabetes, chronic renal disease)
• Patient previously received radiotherapy to ≥ 25% of the bone marrow
• Patient had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery
• Patients with an ECOG Performance Status Score ≥ 3
• Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x IULN, with the exception of patients on treatment with oral anticoagulant
• Patients with known positivity for human immunodeficiency virus (HIV)
• baseline testing for HIV is not required
• Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
• Patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment
• Patients who are chronic users of acetaminophen or medications containing acetaminophen.
• Patients who received acetaminophen or medications containing acetaminophen within 72 hours prior to study entry.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Drug-Drug interaction	Drug: Imatinib/Acetaminophen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To investigate the effects of the co-administration of imatinib on the pharmacokinetics of acetaminophen / paracetamol	Day 1, day 2 -7, Day 8
To investigate the pharmacokinetic characteristics of imatinib at steady state in CML-CP patients following 400 mg dosing co-administered with acetaminophen	Day 1, Day 2-7, Day 8

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: January 29, 2007
• First Submitted That Met QC Criteria: January 29, 2007
• First Posted (Estimate): January 30, 2007

Study Record Updates

• Last Update Posted (Estimate): April 21, 2016
• Last Update Submitted That Met QC Criteria: April 20, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: acetaminophen; Chronic Myeloid Leukemia; CML; Pharmacokinetic; STI571; imatinib; Philadelphia Chromosome
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Antineoplastic Agents; Protein Kinase Inhibitors; Acetaminophen; Imatinib Mesylate
• Other Study ID Numbers: CSTI571A2107