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

December 6, 2020 updated by: Novartis Pharmaceuticals

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Tokyo, Japan
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nilotinib
Drug: Nilotinib
Other Names:
  • AMN107

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
every first 28 days
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
day 1 and 15 of cycle 1,day 6, 8, 10, 12, 22 and 28 of cycle 1, day 15 of cycle 2

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Day 28 cycle 1, 2 and 3, at the time of disease progression, and at the time of study completion
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
Day 28 cycle 1, 2 and 3, at the time of disease progression, and at the time of study comp

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

January 1, 2007

Study Registration Dates

First Submitted

October 5, 2006

First Submitted That Met QC Criteria

October 5, 2006

First Posted (Estimate)

October 6, 2006

Study Record Updates

Last Update Posted (Actual)

December 8, 2020

Last Update Submitted That Met QC Criteria

December 6, 2020

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAMN107A1101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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