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Nilotinib and Imatinib Mesylate in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia

Front-line Treatment of Philadelphia Positive (Ph Pos), BCRABL Positive, Chronic Myeloid Leukemia (CML) With Two Tyrosine Kinase Inhibitors (TKI) (Nilotinib and Imotinib) A Phase II Exploratory Multicentric Centre.

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00769327
Acronym
CML0408
Enrollment
129
Registered
2008-10-09
Start date
2009-02-09
Completion date
2014-10-10
Last updated
2022-01-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia

Keywords

chronic myelogenous leukemia, BCR-ABL1 positive, chronic phase chronic myelogenous leukemia

Brief summary

RATIONALE: Nilotinib and imatinib mesylate 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 giving nilotinib together with imatinib mesylate works in treating patients with early chronic phase chronic myelogenous leukemia.

Detailed description

OBJECTIVES: Primary * To assess the complete cytogenetic response rate at 12 months in patients with Philadelphia chromosome- and BCR-ABL-positive early chronic phase chronic myelogenous leukemia treated with nilotinib and imatinib mesylate. Secondary * To assess the complete cytogenetic response rate at 6 and 24 months in these patients. * To assess the major and complete molecular response rate at 6, 12, and 24 months in these patients. * To assess the frequency and the types of BCR-ABL kinase domain mutations at 24 months during and for 3 years after study treatment. * To assess the rate of failures and the time to failure at 12, 24, and 60 months in these patients. * To assess compliance, toxicity, and adverse events in these patients. * To understand the relationship between response, gene expression profile, biomarkers, and drug plasma concentrations in these patients. OUTLINE: This is a multicenter study. Patients receive oral nilotinib twice daily in months 1-3, 7-9, 13-15, and 19-21 and oral imatinib mesylate once daily in months 4-6, 10-12, 16-18, and 22-24. Treatment continues for 24 months in the absence of disease progression or unacceptable toxicity. Patients may be eligible to continue oral nilotinib and oral imatinib mesylate for up to another 36 months if it is in the interest of the patient. Blood samples and bone marrow biopsies are collected periodically for cytogenetic response by chromosome banding analysis and FISH analysis; real-time quantitative PCR mutational analysis and single nucleotide polymorphism analysis of BCR-ABL transcripts; and gene expression profiling and correlative biomarker studies. After completion of study therapy, patients are followed every 6 months for 3 years and then every 12 months for 5 years.

Interventions

DRUGimatinib mesylate
DRUGnilotinib
GENETICcytogenetic analysis
GENETICfluorescence in situ hybridization
GENETICmicroarray analysis
GENETICmutation analysis
GENETICpolymerase chain reaction
GENETICpolymorphism analysis
OTHERlaboratory biomarker analysis

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Cytologically and cytogenetically confirmed chronic myelogenous leukemia meeting the following criteria: * Early chronic phase disease (\< 6 months from diagnosis) * Philadelphia chromosome-positive disease * BCR-ABL-positive PATIENT CHARACTERISTICS: * WHO performance status 0-1 * ALT and AST = 2.5 times upper limit of normal (ULN) (5.0 times ULN if considered due to leukemia) * Alkaline phosphatase = 2.5 times ULN (unless considered due to leukemia) * Serum bilirubin = 1.5 times ULN * Serum creatinine = 1.5 times ULN * Serum amylase = 1.5 times ULN * Serum lipase = 1.5 times ULN * Normal serum levels of the following or correctable with supplements: * Potassium * Total calcium (corrected for serum albumin) * Magnesium * Phosphorus * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier method contraception during study and for up to 3 months following completion of study treatment * No impaired cardiac function, including any of the following: * LVEF \< 45% by MUGA scan or echocardiogram * Uncontrolled congestive heart failure * Uncontrolled hypertension * Uncontrolled angina pectoris * Myocardial infarction within the past 12 months * No significant electric heart abnormalities, including any of the following: * History or active ventricular or atrial tachyarrhythmias * Congenital long QT syndrome and/or QTc \> 450 msec on screening ECG * No history of acute (within one year) or chronic pancreatitis * No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) * No acute or chronic liver or renal disease considered unrelated to leukemia * No known diagnosis of HIV infection * No other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol * No other primary malignancy that is currently clinically significant or requires active intervention PRIOR CONCURRENT THERAPY: * More than 2 weeks since prior major surgery and recovered * More than 30 days since prior imatinib mesylate, with a washout period of ≥ 7 days * More than 4 weeks since prior investigational drug * No prior hematopoietic stem cell transplantation * No concurrent therapeutic coumarin derivates (i.e., warfarin, acenocoumarol, phenprocoumon) * No concurrent medications that would prolong the QT interval * No concurrent chemotherapy, investigational agents, radiotherapy, or biologic therapy * Prior treatment with hydroxyurea or anagrelide allowed

Design outcomes

Primary

MeasureTime frame
Complete cytogenetic response rateAt 12 months from study entry

Secondary

MeasureTime frame
Major and complete molecular response rateAt at 6, 12 and 24 months from study entry
Development of BCR-ABL kinase domain mutations (number, timing, and type)At at 24 months during and for 3 years after study treatment
Rate of failures and the time to failureAt 12, 24, and 60 months from study entry
Complete cytogenetic responseAt at 6 and 24 months from study entry
Frequency and type of adverse events (AE) and severe AEAt 24 months from study entry
Relationship between response, the gene expression profile, the biomarkers of leukemic cells, and plasma concentrations of nilotinib and imatinib mesylateAt 24 months from study entry
Safety and tolerabilityAt 24 months from study entry

Countries

Italy

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 19, 2026