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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. Identifier: NCT00109707
Recruitment Status : Completed
First Posted : May 3, 2005
Last Update Posted : December 8, 2020
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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)

Condition or disease Intervention/treatment Phase
Chronic Myelogenous Leukemia Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive) Hypereosinophilic Syndrome Systemic Mastocytosis Drug: Nilotinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 942 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Study Start Date : May 2004
Actual Primary Completion Date : September 2012
Actual Study Completion Date : September 2012

Arm Intervention/treatment
Experimental: Arm 1
Relapsed / refractory Ph+ ALL patients
Drug: Nilotinib
Experimental: Arm 2 - Group A and Group B
Imatinib-resistant / intolerant Ph+ CML-BC patients
Drug: Nilotinib
Experimental: Arm 3 - Group A and Group
Imatinib-resistant / intolerant Ph+ CML-AP patients
Drug: Nilotinib
Experimental: Arm 4 - Group A and Group B
Imatinib-resistant / intolerant Ph+ CML-CP patients
Drug: Nilotinib
Experimental: Arm 5
Hypereosinophilic syndrome and chronic eosinophilic leukemia patients
Drug: Nilotinib
Experimental: Arm 6
Systemic Mastocytosis patients
Drug: Nilotinib

Primary Outcome Measures :
  1. • 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 ]
  2. • 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 ]
  3. • 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 ]
  4. • 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 ]

Secondary Outcome Measures :
  1. To assess changes during and after therapy in malignant cells taken from the bone marrow and/or blood.(phase ll) [ Time Frame: study duration ]
  2. To evaluate the population pharmacokinetics of AMN107 (all arms of the study) (phase ll) [ Time Frame: study duration ]
  3. 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 ]
  4. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00109707

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Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticlas Novartis Pharmaceuticals
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals Identifier: NCT00109707    
Other Study ID Numbers: CAMN107A2101
First Posted: May 3, 2005    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: April 2016
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
CML in blast crisis
CML in chronic phase
CML in accelerated phase
Gleevec resistance
Gleevec intolerant
Gleevec and CML
imatinib resistance
imatinib intolerant
Hypereosinophilic Syndrome
Systemic Mastocytosis
Chronic eosinophilic syndrome
Philadelphia chromosome positive acute lymphoblastic leukemia
Ph+ ALL refractory to standard therapy
Ph+ALL relapsed
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mastocytosis, Systemic
Hypereosinophilic Syndrome
Philadelphia Chromosome
Pathologic Processes
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Immune Complex Diseases
Leukocyte Disorders