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

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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 )

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

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
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


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 ClinicalTrials.gov identifier (NCT number): NCT00109707


  Hide Study Locations
Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
Stanford University Medical Center
Stanford, California, United States, 94305-5750
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Dept.of H. Lee Moffitt
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)
Chicago, Illinois, United States, 60637
University of Illinois at Chicago Divisionof Hematology/Oncology
Chicago, Illinois, United States
United States, Indiana
Indiana Blood and Marrow Institute Dept of Indiana Blood&Mar (2)
Beach Grove, Indiana, United States, 46107
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Div.of Hematologic Malignancie
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Health System Clinical Trials Office
Ann Arbor, Michigan, United States, 48109
Wayne State University
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic - Rochester
Rochester, Minnesota, United States, 55905
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute Rosewell SC
Buffalo, New York, United States, 14263
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10017
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Tennessee
The Jones Clinic
Germantown, Tennessee, United States, 38138
Vanderbilt University Medical Center, Clinical Trials Center Investigational Drug Services
Nashville, Tennessee, United States, 37212
United States, Texas
MD Anderson Cancer Center/University of Texas
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Australia, New South Wales
Novartis Investigative Site
St. Leonards, New South Wales, Australia, 2065
Australia, South Australia
Novartis Investigative Site
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Novartis Investigative Site
Prahran, Victoria, Australia, 3181
Austria
Novartis Investigative Site
Wien, Austria, A-1090
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1000
Novartis Investigative Site
Haine-saint-Paul, Belgium, 7100
Novartis Investigative Site
Leuven, Belgium, 3000
Novartis Investigative Site
Yvoir, Belgium, 5530
Canada, British Columbia
Novartis Investigative Site
Vancouver, British Columbia, Canada, V5Z 4E3
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H1T 2M4
Novartis Investigative Site
Montreal, Quebec, Canada, H3A 1A1
Denmark
Novartis Investigative Site
Vejle, Denmark, DK-7100
Finland
Novartis Investigative Site
HUS Helsinki, Finland, FIN-00029
France
Novartis Investigative Site
Bordeaux Cedex, France, 33076
Novartis Investigative Site
Créteil, France, 94010
Novartis Investigative Site
Dijon, France, 21034
Novartis Investigative Site
Lille, France, 59037
Novartis Investigative Site
Limoges cedex, France, 87042
Novartis Investigative Site
Lyon, France, 69437
Novartis Investigative Site
Marseille, France, 13273
Novartis Investigative Site
Poitiers, France, 86021
Novartis Investigative Site
Rennes, France, 35019
Novartis Investigative Site
Vandoeuvre les Nancy, France, 54511
Germany
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Duesseldorf, Germany, 40225
Novartis Investigative Site
Frankfurt/M, Germany, 60590
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Leipzig, Germany, 04103
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Mannheim, Germany, 68169
Novartis Investigative Site
Muenchen, Germany, 81675
Hong Kong
Novartis Investigative Site
Pokfulam, Hong Kong
Italy
Novartis Investigative Site
Bergamo, BG, Italy, 24128
Novartis Investigative Site
Bologna, BO, Italy, 40138
Novartis Investigative Site
Genova, GE, Italy, 16132
Novartis Investigative Site
Monza, MB, Italy, 20900
Novartis Investigative Site
Milano, MI, Italy, 20162
Novartis Investigative Site
Pescara, PE, Italy, 65124
Novartis Investigative Site
Pavia, PV, Italy, 27100
Novartis Investigative Site
Reggio Calabria, RC, Italy, 89124
Novartis Investigative Site
Roma, RM, Italy, 00144
Novartis Investigative Site
Roma, RM, Italy, 00161
Novartis Investigative Site
Roma, RM, Italy, 00168
Novartis Investigative Site
Orbassano, TO, Italy, 10043
Novartis Investigative Site
Napoli, Italy, 80131
Korea, Republic of
Novartis Investigative Site
Hwasun-gun, Jeollanam-do, Korea, Republic of, 519-809
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 05505
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 137-701
Novartis Investigative Site
Taegu, Korea, Republic of, 700 - 721
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1081 HV
Novartis Investigative Site
Rotterdam, Netherlands
New Zealand
Novartis Investigative Site
Grafton, Auckland, New Zealand
Norway
Novartis Investigative Site
Oslo, Norway, NO-0310
Poland
Novartis Investigative Site
Katowice, Poland, 40-635
Novartis Investigative Site
Lodz, Poland, 90-153
Novartis Investigative Site
Warszawa, Poland, 02-097
Novartis Investigative Site
Warszawa, Poland, 02-776
Novartis Investigative Site
Wroclaw, Poland, 50-367
Singapore
Novartis Investigative Site
Singapore, Singapore, 169608
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
Sweden
Novartis Investigative Site
Göteborg, Sweden, SE-413 45
Novartis Investigative Site
Linköping, Sweden, SE-581 85
Novartis Investigative Site
Lund, Sweden, SE-221 85
Novartis Investigative Site
Uppsala, Sweden, SE-751 85
Switzerland
Novartis Investigative Site
Basel, Switzerland, 4031
Novartis Investigative Site
Genève, Switzerland, 1211
Taiwan
Novartis Investigative Site
Niaosong Township, Taiwan, 83301
United Kingdom
Novartis Investigative Site
Birmingham, United Kingdom, B15 2TH
Novartis Investigative Site
Cambridge, United Kingdom, CB2 2QQ
Novartis Investigative Site
Glasgow - Scotland, United Kingdom, G12 OYN
Novartis Investigative Site
Leeds, United Kingdom, LS9 7TF
Novartis Investigative Site
Liverpool, United Kingdom, L7 8XP
Novartis Investigative Site
London, United Kingdom, SE5 9RS
Novartis Investigative Site
London, United Kingdom, W12 0NN
Novartis Investigative Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticlas Novartis Pharmaceuticals

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00109707     History of Changes
Other Study ID Numbers: CAMN107A2101
First Posted: May 3, 2005    Key Record Dates
Last Update Posted: April 29, 2016
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
HES
CEL
CML
SM
Ph+ ALL refractory to standard therapy
Ph+ALL relapsed
AMN107A

Additional relevant MeSH terms:
Syndrome
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Mastocytosis
Mastocytosis, Systemic
Blast Crisis
Hypereosinophilic Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
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
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes