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A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT00109707
Recruitment Status : Completed
First Posted : May 3, 2005
Results First Posted : June 29, 2021
Last Update Posted : June 29, 2021
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 : 507 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.
Actual Study Start Date : April 2005
Actual Primary Completion Date : September 2012
Actual Study Completion Date : September 2012

Arm Intervention/treatment
Experimental: CML-CP With Prior Imatinib Only
Imatinib-resistant / intolerant PH+ CML-CP patients
Drug: Nilotinib
Experimental: CML-AP With Prior Imatinib Onl
Imatinib-resistant / intolerant PH+ CML-AP patients
Drug: Nilotinib
Experimental: CML-CP
Imatinib-resistant / intolerant PH+ CML-CP patients
Drug: Nilotinib

Primary Outcome Measures :
  1. Number of Participants With Major Cytogenetic Response (MCyR) [ Time Frame: Up to End of the Treatment (Approximately 7.5 years) ]
    Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).

  2. Number of Participants Confirmed Overall Hematological Response (Phase II) [ Time Frame: Up to End of the Treatment (Approximately 7.5 years) ]

    Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).

    Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.

Secondary Outcome Measures :
  1. Number of Participants With Overall Major Cytogenetic Responses (Phase II) [ Time Frame: Up to End of the Treatment (Approximately 7.5 years) ]
    Cytogenetic responses (CyRs) in CML are based on the percentage of Ph+ metaphases in bone marrow; a value of 0% Ph+ metaphases defines a complete cytogenetic response (CCyR) and >0% to 35% defines a major cytogenetic response (MCyR). Achievement of CCyR is associated with a significant survival advantage in participants with CML-CP. MCyR was categorized as either CCyR or partial cytogenetic response (PCyR).

  2. Number of Participants With Complete Hematologic Response (Phase II) [ Time Frame: Up to End of the Treatment (Approximately 7.5 years) ]
    A Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; < 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.

  3. Participants With (MMR) Major Molecular Response (Phase II) [ Time Frame: Up to End of the Treatment (Approximately 7.5 years) ]
    MMR was defined for participants who demonstrated a reduction in BCR-ABL/control gene % transcripts to ≤0.1% based on international scale. The control gene used may have been either BCR or ABL.

  4. Time to Progression (TTP) (Phase II) [ Time Frame: Up to End of the Treatment (Approximately 7.5 years) ]

    Time to Progression was defined as the time from the start of nilotinib to the earliest date of Disease Progression (PD), discontinuation due to PD or death.

    Disease progression was defined as an increase in the number of circulating leukemic cells via cytogenetic assessment using real-time quantitative reverse transcriptase polymerase chain reaction (PCR).

  5. Overall Survival (OS) (Phase II) [ Time Frame: Up to End of the Treatment (Approximately 7.5 years) ]
    OS was calculated for all participants as the time between the start of nilotinib and death. Participants were followed for survival after discontinuation, every 3 months, and were included in the analysis of OS. Censoring was at the date of the last contact for discontinued participants and followed up for survival.

  6. Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety [ Time Frame: From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years) ]
    Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

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 ClinicalTrials.gov 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 ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00109707    
Other Study ID Numbers: CAMN107A2101
First Posted: May 3, 2005    Key Record Dates
Results First Posted: June 29, 2021
Last Update Posted: June 29, 2021
Last Verified: June 2021
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
Hematologic Neoplasms
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
Neoplasms by Site
Translocation, Genetic
Chromosome Aberrations
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Immune Complex Diseases