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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00109707
First received: May 2, 2005
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • • 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 ] [ Designated as safety issue: Yes ]
  • • 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 ] [ Designated as safety issue: Yes ]
  • • 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 ] [ Designated as safety issue: Yes ]
  • • 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 ] [ Designated as safety issue: Yes ]

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

Enrollment: 942
Study Start Date: May 2004
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00109707

  Show 101 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticlas Novartis Pharmaceuticals
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00109707     History of Changes
Other Study ID Numbers: CAMN107A2101
Study First Received: May 2, 2005
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Canada: Health Canada

Keywords provided by Novartis:
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
HES
CEL
CML
SM
Ph+ ALL refractory to standard therapy
Ph+ALL relapsed
AMN107A

Additional relevant MeSH terms:
Blast Crisis
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mastocytosis
Urticaria Pigmentosa
Philadelphia Chromosome
Hypereosinophilic Syndrome
Mastocytosis, Systemic
Neoplasms by Histologic Type
Neoplasms
Cell Transformation, Neoplastic
Neoplastic Processes
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Pathologic Processes
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Mastocytosis, Cutaneous
Pigmentation Disorders
Translocation, Genetic
Chromosome Aberrations

ClinicalTrials.gov processed this record on April 22, 2014