A Phase l/ll Study of AMN107 in Adult Patients With Glivec-intolerant CML or Relapsed-refractory Ph+ALL

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00384228
First received: October 5, 2006
Last updated: April 11, 2012
Last verified: April 2012
  Purpose

This study will investigate if nilotinib provides an improved safety and efficacy profile over that seen in patients receiving Imatinib.


Condition Intervention Phase
Chronic Myelogenous Leukemia
Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)
Drug: Nilotinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Multicenter, Dose-escalation Study of Oral Nilotinib on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant or Imatinib-intolerant CML, or Relapse/Refractory Ph+ALL

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Safety evaluation assessed by dose limiting toxicity within first cycle of 28 day treatment and AEs within 3 cycles [ Time Frame: every first 28 days ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) profile of single and multiple doses [ Time Frame: day 1 and 15 of cycle 1,day 6, 8, 10, 12, 22 and 28 of cycle 1, day 15 of cycle 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Anti-leukemic activity within 3 cycles of 28 days treatment [ Time Frame: Day 28 cycle 1, 2 and 3, at the time of disease progression, and at the time of study completion ] [ Designated as safety issue: No ]
  • Bone marrow and/or blood assessments to detect the presence of Bcr-Abl transcript and mutational analysis of Bcr-Abl before, during and after therapy. [ Time Frame: Day 28 cycle 1, 2 and 3, at the time of disease progression, and at the time of study comp ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: May 2005
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib Drug: Nilotinib
Other Name: AMN107

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed as Ph+ ALL who are either relapsed after or refractory to standard therapy
  • Diagnosed as CML in blast crisis or accelerated phase or chronic phase who are resistant or intolerant to imatinib
  • Performance status is normal or ambulatory and capable of all self-care Exclusion Criteria
  • A history of significant or serious uncontrolled cardiovascular disease
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of nilotinib
  • Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control

Exclusion Criteria:

  • Cytopathologically confirmed CNS infiltration NB: in absence of suspicion of CNS involvement, lumbar puncture is not required
  • Impaired cardiac function, including any one of the following

    • LVEF < 45% as determined by echocardiogram
    • Complete left bundle branch block
    • Use of a cardiac pacemaker
    • ST depression of > 1mm in 2 or more leads and/or T-wave inversions in 2 or more contiguous leads
    • Congenital long QT syndrome
    • History of or presence of significant ventricular or atrial tachyarrhythmias
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTc > 480 msec on screening ECG (using the QTcF formula)
    • Right bundle branch block plus left anterior hemiblock, bifascicular block
    • Myocardial infarction within 3 months prior to starting AMN107
    • Uncontrolled angina pectoris
  • Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of AMN107 (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Use of therapeutic warfarin
  • Acute or chronic liver or renal disease considered unrelated to tumor (e.g., hepatitis, cirrhosis, renal insufficiency, etc.)
  • 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
  • Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF) ≤ 1 week prior to starting study drug.
  • Patients who are currently receiving treatment with any of the medications listed in (cf. Post-text suppl. 5) that cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in (cf. Post-text suppl. 5) have the potential to prolong the Q-T interval.
  • Patients who have received chemotherapy ≤ 1 week or who are within 5 half-lives of their last dose chemotherapy (6 weeks for nitrosurea or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy. Hydroxyurea is permitted at the investigator's discretion prior to enrollment.
  • Patients who have received Glivec® ≤ 1 week or who have not recovered from side effects of such therapy.
  • Patients who have received immunotherapy ≤ 1 week prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patients who have received any investigational drug (excluding STI571/Glivec) ≤ 4 weeks or investigational cytotoxic agent within 1 week (or who are within 5 half-lives of a previous investigational cytotoxic agent) prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patients who have received wide field radiotherapy ≤ 4 week or limited field radiation for palliation ≤ 2 week prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of AMN107). Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug
  • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
  • Patients unwilling or unable to comply with the protocol

Other protocol-defined inclusion and exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00384228

Locations
Japan
Novartis Investigative Site
Tokyo, Japan
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00384228     History of Changes
Other Study ID Numbers: CAMN107A1101
Study First Received: October 5, 2006
Last Updated: April 11, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Novartis:
Chronic Myelogenous Leukemia
Acute Lymphoblastic Leukemia

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Abnormal Karyotype
Philadelphia Chromosome
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Chromosome Aberrations
Pathologic Processes
Translocation, Genetic

ClinicalTrials.gov processed this record on September 16, 2014