Status:

COMPLETED

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

Lead Sponsor:

Novartis Pharmaceuticals

Conditions:

Chronic Myelogenous Leukemia

Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)

Eligibility:

All Genders

20+ years

Phase:

PHASE1

PHASE2

Brief Summary

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

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

May 1 2005

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

Estimated Enrollment :

42 Patients enrolled

Trial Details

Trial ID

NCT00384228

Start Date

May 1 2005

Last Update

December 8 2020

Active Locations (1)

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Page 1 of 1 (1 locations)

1

Novartis Investigative Site

Tokyo, Japan