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A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Blood Related Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00109707
Recruitment Status : Completed
First Posted : May 3, 2005
Last Update Posted : April 29, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 2, 2005
First Posted Date  ICMJE May 3, 2005
Last Update Posted Date April 29, 2016
Study Start Date  ICMJE May 2004
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2010)
  • • To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of AMN107 as a single agent when administered as an oral once-daily and twice daily dose to adult patients with imatinib-resistant CML (phase l) [ Time Frame: study duration ]
  • • To characterize the pharmacokinetic profile of AMN107 in serum and, where samples are available, in tumor cells and normal hematopoietic cells. (phase l) [ Time Frame: duration of study ]
  • • To evaluate the efficacy and safety of AMN107 in patients with imatinib-resistant or intolerant CML-BC, imatinib-resistant or intolerant CML-AP and imatinib-resistant or intolerant CML-CP. (phase ll) [ Time Frame: duration of study ]
  • • To evaluate safety and preliminary anticancer activity of AMN107 in relapsed/refractory patients with Ph+ ALL, HES/CEL and SM. (phase ll) [ Time Frame: duration of study ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00109707 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2010)
  • To assess changes during and after therapy in malignant cells taken from the bone marrow and/or blood.(phase ll) [ Time Frame: study duration ]
  • To evaluate the population pharmacokinetics of AMN107 (all arms of the study) (phase ll) [ Time Frame: study duration ]
  • To examine whether individual genetic variation in genes relating to drug metabolism, CML and the drug pathway confer differential response to AMN107 (phase ll) [ Time Frame: study duration ]
  • To identify gene expression patterns in tumor cells that are associated with treatment response to AMN107 or that correlate with the severity or progression of CML. (phase ll) [ Time Frame: study duration ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Blood Related Cancers
Official Title  ICMJE A Phase IA/II Multicenter, Dose-escalation Study of Oral AMN107 on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant/Intolerant CML in Chronic or Accelerated Phase or Blast Crisis, Relapsed/Refractory Ph+ ALL, and Other Hematologic Malignancies.
Brief Summary

The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions:

Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1)

Group A - Imatinib failure only (arms 2, 3 and 4)

  • imatinib-resistant or intolerant CML - Chronic Phase (CP)
  • imatinib-resistant or intolerant CML - Accelerated Phase (AP)
  • imatinib-resistant or intolerant CML - Blast Crisis (BC)

Group B - Imatinib and other TKI failure (arms 2, 3 and 4)

  • imatinib-resistant or intolerant CML - Chronic Phase (CP)
  • imatinib-resistant or intolerant CML - Accelerated Phase (AP)
  • imatinib-resistant or intolerant CML - Blast Crisis (BC)

Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5)

Systemic mastocytosis (Sm) (arm 6)

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Myelogenous Leukemia
  • Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)
  • Hypereosinophilic Syndrome
  • Systemic Mastocytosis
Intervention  ICMJE Drug: Nilotinib
Study Arms  ICMJE
  • Experimental: Arm 1
    Relapsed / refractory Ph+ ALL patients
    Intervention: Drug: Nilotinib
  • Experimental: Arm 2 - Group A and Group B
    Imatinib-resistant / intolerant Ph+ CML-BC patients
    Intervention: Drug: Nilotinib
  • Experimental: Arm 3 - Group A and Group
    Imatinib-resistant / intolerant Ph+ CML-AP patients
    Intervention: Drug: Nilotinib
  • Experimental: Arm 4 - Group A and Group B
    Imatinib-resistant / intolerant Ph+ CML-CP patients
    Intervention: Drug: Nilotinib
  • Experimental: Arm 5
    Hypereosinophilic syndrome and chronic eosinophilic leukemia patients
    Intervention: Drug: Nilotinib
  • Experimental: Arm 6
    Systemic Mastocytosis patients
    Intervention: Drug: Nilotinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 9, 2013)
942
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
530
Actual Study Completion Date  ICMJE September 2012
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Main inclusion criteria include:

  • Patients with CML in blast crisis, CML in accelerated phase defined as never in blast crisis phase, or CML in chronic phase defined as never been in blast crisis phase or accelerated phase who have: *developed progressive disease during therapy with at least 600 mg of imatinib per day, -OR- *patients with CML on imatinib therapy, at any dose, developing progressive disease and the presence of a genetic mutation likely to result in imatinib resistance -OR- *have developed an intolerance to imatinib
  • Relapsed or refractory Ph+ ALL
  • Hypereosinophilic syndrome/chronic eosinophilic leukemia.
  • Systemic mastocytosis who have a clinical indication for treatment.
  • Prior imatinib therapy for patients with Ph+ ALL, HES/CEL and SM is permitted but is not required
  • CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition of imatinib-resistance or intolerance are eligible
  • Written informed consent prior to any study procedures being performed

Exclusion Criteria:

  • Impaired cardiac function
  • Patients with severe/chronic or uncontrolled medical conditions (including but not limited to diabetes, infections, GI impairment, CNS infiltration, liver and kidney disease)
  • Prior and concomitant use of certain medications (including but not limited to warfarin, chemotherapy, hematopoietic colony-stimulating growth factors, medications that can affect electrocardiogram test results, other investigational drugs )
  • Women who are pregnant or breastfeeding
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
  • Patients unwilling to comply with the protocol.
  • Known diagnosis of human immunodeficiency virus (HIV) infection

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Denmark,   Finland,   France,   Germany,   Hong Kong,   Italy,   Korea, Republic of,   Netherlands,   New Zealand,   Norway,   Poland,   Singapore,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00109707
Other Study ID Numbers  ICMJE CAMN107A2101
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticlas Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP