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

Cancer Trials Ireland

Status and phase

Completed

Phase 2

Conditions

Leukemia

Treatments

Genetic: polymerase chain reaction

Drug: nilotinib

Other: pharmacological study

Genetic: cytogenetic analysis

Genetic: mutation analysis

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00809211

EU-20899

ICORG 08-02

EUDRACT-2008-004551-30

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 estimated patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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