Nilotinib in Treating Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

NCT ID: NCT00809211

Last Updated: 2018-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2016-02-29

Brief Summary

RATIONALE: Nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well nilotinib works in treating patients with newly diagnosed chronic phase chronic myelogenous leukemia.

Detailed Description

OBJECTIVES:

Primary

• To establish the complete cytogenetic response rate at 6 months in patients with newly diagnosed Philadelphia chromosome-positive chronic phase chronic myelogenous leukemia treated with nilotinib.

Secondary

• To establish the complete cytogenetic response rate at 3, 9, 12, 18, and 24 months in these patients.
• To establish the molecular response rate at 3, 6, 9, 12, 18, and 24 months in these patients.
• To establish the safety of this drug in these patients.
• To correlate pharmacokinetic data with response rate and toxicity.
• To correlate Bcr-Abl results using GeneXpert with Bcr-Abl results using international standardized quantitative PCR.
• To estimate the prevalence of Bcr-Abl mutations prior to and during treatment.

OUTLINE: This is a multicenter study.

Patients receive oral nilotinib twice daily on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Peripheral blood and bone marrow samples are collected periodically for mutation analysis, Bcr-Abl analysis by quantitative PCR, metaphase cytogenetics, and pharmacokinetic analysis.

After completion of study therapy, patients are followed every 3 months for 2 years.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nilotinib

Group Type: EXPERIMENTAL

nilotinib

Intervention Type: DRUG

cytogenetic analysis

Intervention Type: GENETIC

mutation analysis

Intervention Type: GENETIC

polymerase chain reaction

Intervention Type: GENETIC

pharmacological study

Intervention Type: OTHER

Interventions

nilotinib

Intervention Type: DRUG

cytogenetic analysis

Intervention Type: GENETIC

mutation analysis

Intervention Type: GENETIC

polymerase chain reaction

Intervention Type: GENETIC

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Cytogenetically confirmed chronic myelogenous leukemia (CML) by standard conventional cytogenetic analysis of bone marrow*

• Newly diagnosed disease (within the past 6 months) NOTE: *FISH cannot be used
• In chronic phase, as defined by the following:

• Less than 15% blasts in peripheral blood and bone marrow
• Less than 30% blasts plus promyelocytes in peripheral blood and bone marrow
• Less than 20% basophils in peripheral blood
• Platelet count ≥ 100,000/mm^3
• No evidence of extramedullary leukemic involvement, except for hepatosplenomegaly
• Philadelphia chromosome-positive disease as demonstrated by (9;22) translocation (presence of Bcr-Abl)

• A review of ≥ 20 metaphases is required
• No previously documented T315I mutations

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Total bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT < 2.5 times ULN
• Estimated glomerular filtration rate ≥ 30 mL/min
• Serum amylase and lipase ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN (unless related to CML)
• Potassium ≥ lower limit of normal (LLN)
• Magnesium ≥ LLN
• Phosphorous ≥ LLN
• Total calcium ≥ LLN (corrected for serum albumin)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No impaired cardiac function including, but not limited to, any of the following:

• LVEF < 45% or < LLN by ECHO
• Inability to determine the QT interval on ECG
• Complete left bundle branch block
• Congenital long QT syndrome or a known family history of long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (< 50 beats/min)
• QTc > 450 msec on an average of 3 serial baseline ECGs (using the QTcF formula)
• Clinically documented myocardial infraction within the past 12 months
• Unstable angina within the past 12 months
• Other clinically significant heart disease (e.g., congestive heart failure or uncontrolled hypertension)
• No severe or uncontrolled medical condition (e.g., uncontrolled diabetes or active or uncontrolled infection)
• No history of significant congenital or acquired bleeding disorder unrelated to CML
• No history of non-compliance to medical regimens
• No other primary malignancy unless it is neither currently clinically significant nor requiring active intervention
• No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
• No acute pancreatitis within the past year
• No history of chronic pancreatitis
• No acute or chronic liver, pancreatic, or severe renal disease considered unrelated to CML

PRIOR CONCURRENT THERAPY:

• No prior therapy for CML other than hydroxyurea and/or anagrelide
• Prior imatinib mesylate allowed provided it was administered for ≤ 14 days
• More than 30 days since prior and no other concurrent investigational agents
• More than 4 weeks since prior major surgery and recovered
• No other concurrent anticancer agents, including chemotherapy and biologic agents
• No concurrent strong CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil)
• No concurrent strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's wort)
• No concurrent medications that have the potential to prolong QT interval
• No concurrent grapefruit, star fruit, Seville oranges, or their derivatives

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Trials Ireland

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mike O'Dwyer, MD

Role: PRINCIPAL_INVESTIGATOR

University College London Hospitals

Locations

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Universitätsklinikum Charité Berlin

Berlin, , Germany

Belfast City Hospital

Belfast, , Ireland

St. James's Hospital

Dublin, , Ireland

University College Hospital

Galway, , Ireland

Chaim Sheba Medical Centre

Tel Litwinsky, , Israel

Countries

United States; Germany; Ireland; Israel

Other Identifiers

ICORG 08-02

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-004551-30

Identifier Type: -

Identifier Source: secondary_id

EU-20899

Identifier Type: -

Identifier Source: secondary_id

ICORG 08-02

Identifier Type: -

Identifier Source: org_study_id