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

NCT00809211 | Completed Phase 2

• 3 other identifiers: ICORG 08-02EUDRACT-2008-004551-30EU-20899
• Study Type: interventional
• Target: 40
• Locations: 4 countries
• Sites: 6

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.

Conditions

Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Complete cytogenetic response rate at 6 months as assessed by metaphase analysis

  6 months

Secondary Outcomes (7)

• Molecular response rate at 3, 6, 9, 12, 18, and 24 months as assessed by quantitative PCR

  6 months

• Time to disease progression

  6 months

• Duration of event-free survival

  6 months

• Overall toxicity rate

  6 months

• Correlation of pharmacokinetic data with response rate and toxicity

  6 months

Study Arms (1)

Nilotinib

EXPERIMENTAL

Drug: nilotinib; Genetic: cytogenetic analysis; Genetic: mutation analysis; Genetic: polymerase chain reaction; Other: pharmacological study

Interventions

nilotinib DRUG

Nilotinib

cytogenetic analysis GENETIC

Nilotinib

mutation analysis GENETIC

Nilotinib

polymerase chain reaction GENETIC

Nilotinib

pharmacological study OTHER

Nilotinib

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (6)

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

Universitätsklinikum Charité Berlin

Berlin, Germany

Location

Belfast City Hospital

Belfast, Ireland

Location

St. James's Hospital

Dublin, 8, Ireland

Location

University College Hospital

Galway, Ireland

Location

Chaim Sheba Medical Centre

Tel Litwinsky, Israel

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase

Interventions

nilotinib; Cytogenetic Analysis; Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Nucleic Acid Amplification Techniques

Study Officials

• Mike O'Dwyer, MD

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2008
• First Posted: December 17, 2008
• Study Start: October 1, 2008
• Primary Completion: May 1, 2011
• Study Completion: February 1, 2016
• Last Updated: July 24, 2018

Record last verified: 2018-07

Locations

IL (1); DE (1); IE (3); US (1)