Efficacy of 400 Mg Versus 800 Mg Imatinib in Chronic Myeloid Leukemia in Chronic Phase Patients - TOPS (Tyrosine Kinase Inhibitor Optimization and Selectivity)

Novartis

Status and phase: Terminated; Phase 3

Conditions: Leukemia, Myeloid, Chronic Phase

Treatments: Drug: Imatinib mesylate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00124748

CSTI571K2301

Details and patient eligibility

About

This study investigated the safety and efficacy of 400mg Versus 800mg imatinib in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase (CML-CP) using molecular endpoints.

Enrollment: 476 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients within 6 months of diagnosis (date of initial diagnosis is the date of first cytogenetic analysis)

• Diagnosis of chronic myelogenous leukemia (CML) in chronic phase with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations and presence of Breakpoint cluster region gene-abelson proto-oncogene (Bcr-Abl)

• Documented chronic phase CML

• Adequate end organ function as defined by:

  • total bilirubin < 1.5 x Upper Limit of Normal (ULN)
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x ULN
  • creatinine < 1.5 x ULN

Exclusion criteria

• Patients in late chronic phase, accelerated phase, or blastic phase are excluded
• Patients who have received other investigational agents
• Patients who received Gleevec/Glivec for any duration prior to study entry, with the exception of those patients successfully completing [CSTI571A2107 (NCT00428909)] study immediately prior to the participation in this study
• 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: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) 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 Eastern Cooperative Oncology Group (ECOG) Performance Status Score ≥ 3
• Patients with International normalized ratio (INR) or partial thromboplastin time (PTT) > 1.5 x ULN, with the exception of patients on treatment with oral anticoagulants
• Patients with known positivity for human immunodeficiency virus (HIV); baseline testing for HIV is not required
• Patients with identified sibling donors where allogeneic bone marrow transplant is elected as first line treatment

Other protocol-defined inclusion/exclusion criteria applied.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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476 participants in 2 patient groups

Imatinib 400 mg

Experimental group

Description:

Oral dose of 400mg Imatinib once daily. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted, reduced, or escalated based on guidelines defined in protocol.

Treatment:

Drug: Imatinib mesylate

imatinib 800 mg

Experimental group

Description:

Patients randomized to receive 800 mg Imatinib were to receive 400 mg twice daily (b.i.d.) oral administration, in the morning and the evening. All patients received the assigned dose starting on Day 0 (Visit 3). The dose of Imatinib could be interrupted or reduced based on guidelines defined in protocol.

Treatment:

Drug: Imatinib mesylate