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

June 8, 2021 updated by: Novartis Pharmaceuticals

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.

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

507

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • St. Leonards, New South Wales, Australia, 2065
        • Novartis Investigative Site
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Novartis Investigative Site
    • Victoria
      • Prahran, Victoria, Australia, 3181
        • Novartis Investigative Site
  • Austria
      • Wien, Austria, A-1090
        • Novartis Investigative Site
  • Belgium
      • Bruxelles, Belgium, 1000
        • Novartis Investigative Site
      • Haine-saint-Paul, Belgium, 7100
        • Novartis Investigative Site
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
      • Yvoir, Belgium, 5530
        • Novartis Investigative Site
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E3
        • Novartis Investigative Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H3A 1A1
        • Novartis Investigative Site
  • Denmark
      • Vejle, Denmark, DK-7100
        • Novartis Investigative Site
  • Finland
      • HUS Helsinki, Finland, FIN-00029
        • Novartis Investigative Site
  • France
      • 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
        • Novartis Investigative Site
  • Germany
      • 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
        • Novartis Investigative Site
  • Hong Kong
      • Pokfulam, Hong Kong
        • Novartis Investigative Site
  • Italy
      • Napoli, Italy, 80131
        • Novartis Investigative Site
    • BG
      • Bergamo, BG, Italy, 24128
        • Novartis Investigative Site
    • BO
      • Bologna, BO, Italy, 40138
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italy, 16132
        • Novartis Investigative Site
    • MB
      • Monza, MB, Italy, 20900
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20162
        • Novartis Investigative Site
    • PE
      • Pescara, PE, Italy, 65124
        • Novartis Investigative Site
    • PV
      • Pavia, PV, Italy, 27100
        • Novartis Investigative Site
    • RC
      • Reggio Calabria, RC, Italy, 89124
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italy, 00168
        • Novartis Investigative Site
      • Roma, RM, Italy, 00144
        • Novartis Investigative Site
      • Roma, RM, Italy, 00161
        • Novartis Investigative Site
    • TO
      • Orbassano, TO, Italy, 10043
        • Novartis Investigative Site
  • Korea, Republic of
      • Taegu, Korea, Republic of, 700 - 721
        • Novartis Investigative Site
    • Jeollanam-do
      • Hwasun-gun, Jeollanam-do, Korea, Republic of, 519-809
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Korea, Republic of, 05505
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republic of, 137-701
        • Novartis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Novartis Investigative Site
      • Rotterdam, Netherlands
        • Novartis Investigative Site
  • New Zealand
    • Auckland
      • Grafton, Auckland, New Zealand
        • Novartis Investigative Site
  • Norway
      • Oslo, Norway, NO-0310
        • Novartis Investigative Site
  • Poland
      • 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
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 169608
        • Novartis Investigative Site
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
      • Hospitalet de LLobregat, Catalunya, Spain, 08907
        • Novartis Investigative Site
  • Sweden
      • 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
        • Novartis Investigative Site
  • Switzerland
      • Basel, Switzerland, 4031
        • Novartis Investigative Site
      • Genève, Switzerland, 1211
        • Novartis Investigative Site
  • Taiwan
      • Niaosong Township, Taiwan, 83301
        • Novartis Investigative Site
  • United Kingdom
      • 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
        • Novartis Investigative Site
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • Stanford, California, United States, 94305-5750
        • Stanford University Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University Of Colorado Hospital
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute Dept.of H. Lee Moffitt
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)
      • Chicago, Illinois, United States
        • University of Illinois at Chicago Divisionof Hematology/Oncology
    • Indiana
      • Beech Grove, Indiana, United States, 46107
        • Indiana Blood and Marrow Institute Dept of Indiana Blood&Mar (2)
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Div.of Hematologic Malignancie
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Health System Clinical Trials Office
      • Detroit, Michigan, United States, 48201
        • Wayne State University
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - Rochester
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute Rosewell SC
      • New York, New York, United States, 10017
        • Memorial Sloan Kettering Cancer Center
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Baptist Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health Sciences University
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • The Jones Clinic
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt University Medical Center, Clinical Trials Center Investigational Drug Services
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center/University of Texas
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Up to End of the Treatment (Approximately 7.5 years)
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.
Up to End of the Treatment (Approximately 7.5 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Up to End of the Treatment (Approximately 7.5 years)
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.
Up to End of the Treatment (Approximately 7.5 years)
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.
Up to End of the Treatment (Approximately 7.5 years)
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).
Up to End of the Treatment (Approximately 7.5 years)
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.
Up to End of the Treatment (Approximately 7.5 years)
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.
From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticlas, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2005

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

September 1, 2012

Study Registration Dates

First Submitted

May 2, 2005

First Submitted That Met QC Criteria

May 2, 2005

First Posted (Estimate)

May 3, 2005

Study Record Updates

Last Update Posted (Actual)

June 29, 2021

Last Update Submitted That Met QC Criteria

June 8, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAMN107A2101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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