Nilotinib and Imatinib Mesylate in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia - Full Text View

Sponsored by:	Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00769327

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: imatinib mesylate Drug: nilotinib Procedure: cytogenetic analysis Procedure: fluorescence in situ hybridization Procedure: gene expression profiling Procedure: laboratory biomarker analysis Procedure: mutation analysis Procedure: polymerase chain reaction Procedure: polymorphism analysis	Phase II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Imatinib Imatinib mesylate Tyrosine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	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.

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete cytogenetic response rate at 12 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete cytogenetic response at 6 and 24 months [ Designated as safety issue: No ]
Major and complete molecular response rate at 6, 12, and 24 months [ Designated as safety issue: No ]
Development of BCR-ABL kinase domain mutations (number, timing, and type) at 24 months during and for 3 years after study treatment [ Designated as safety issue: No ]
Rate of failures and the time to failure at 12, 24, and 60 months [ Designated as safety issue: No ]
Safety and tolerability [ Designated as safety issue: Yes ]
Frequency and type of adverse events (AE) and severe AE [ Designated as safety issue: Yes ]
Relationship between response, the gene expression profile, the biomarkers of leukemic cells, and plasma concentrations of nilotinib and imatinib mesylate [ Designated as safety issue: No ]

Estimated Enrollment:	114
Study Start Date:	November 2008

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00769327

Sponsors and Collaborators

Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

Principal Investigator:

Michele Baccarani, MD

Gruppo Italiano Malattie EMatologiche dell'Adulto

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000615008, GIMEMA-CML0408, EUDRACT-2008-004384-19, EU-20881
Study First Received:	October 8, 2008
Last Updated:	October 8, 2008
ClinicalTrials.gov Identifier:	NCT00769327
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

Philadelphia chromosome positive chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia

Study placed in the following topic categories:

Imatinib
Philadelphia Chromosome
Leukemia
Chronic myelogenous leukemia
Hematologic Diseases

Myeloproliferative Disorders
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid
Bone Marrow Diseases

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009