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 : December 8, 2020
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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
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Drug: Nilotinib |
Experimental: Arm 3 - Group A and Group
Imatinib-resistant / intolerant Ph+ CML-AP patients
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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
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Drug: Nilotinib |
- • 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 ]
- 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 ]

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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

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

Study Director: | Novartis Pharmaceuticlas | Novartis Pharmaceuticals |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov 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 |
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 |
Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Mastocytosis Mastocytosis, Systemic Hypereosinophilic Syndrome Syndrome Philadelphia Chromosome 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 Immune Complex Diseases Hypersensitivity Eosinophilia Leukocyte Disorders |