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Chronic Myelogenous LeukemiaPhase 1/2NCT00109707

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

A Phase 1/2 study testing Nilotinib in people with Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive), run by Novartis Pharmaceuticals at 101 sites in 22 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nilotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
507 participants
Where
101 sitesin 22 countries
Study dates
Apr 2005to Sep 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

101 sites in 22 countries.

101 sites in 22 countries

United States24 sites

  • University of Michigan Health System Clinical Trials Office

    Ann Arbor, Michigan, 48109

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Div.of Hematologic Malignancie

    Baltimore, Maryland, 21231

  • Indiana Blood and Marrow Institute Dept of Indiana Blood&Mar (2)

    Beech Grove, Indiana, 46107

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Roswell Park Cancer Institute Rosewell SC

    Buffalo, New York, 14263

  • University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)

    Chicago, Illinois, 60637

  • University of Illinois at Chicago Divisionof Hematology/Oncology

    Chicago, Illinois

  • Wayne State University

    Detroit, Michigan, 48201

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • The Jones Clinic

    Germantown, Tennessee, 38138

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center/University of Texas

    Houston, Texas, 77030

  • Vanderbilt University Medical Center, Clinical Trials Center Investigational Drug Services

    Nashville, Tennessee, 37212

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10017

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55905

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Swedish Cancer Institute

    Seattle, Washington, 98104

  • Stanford University Medical Center

    Stanford, California, 94305-5750

  • H. Lee Moffitt Cancer Center & Research Institute Dept.of H. Lee Moffitt

    Tampa, Florida, 33612

  • Wake Forest University Baptist Medical Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

Italy13 sites

  • Novartis Investigative Site

    Bergamo, BG, 24128

  • Novartis Investigative Site

    Bologna, BO, 40138

  • Novartis Investigative Site

    Genova, GE, 16132

  • Novartis Investigative Site

    Milan, MI, 20162

  • Novartis Investigative Site

    Monza, MB, 20900

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Orbassano, TO, 10043

  • Novartis Investigative Site

    Pavia, PV, 27100

  • Novartis Investigative Site

    Pescara, PE, 65124

  • Novartis Investigative Site

    Reggio Calabria, RC, 89124

  • Novartis Investigative Site

    Roma, RM, 00144

  • Novartis Investigative Site

    Roma, RM, 00161

  • Novartis Investigative Site

    Roma, RM, 00168

Other trials in Italy

France10 sites

  • Novartis Investigative Site

    Bordeaux, 33076

  • Novartis Investigative Site

    Créteil, 94010

  • Novartis Investigative Site

    Dijon, 21034

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Limoges, 87042

  • Novartis Investigative Site

    Lyon, 69437

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Poitiers, 86021

  • Novartis Investigative Site

    Rennes, 35019

  • Novartis Investigative Site

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Germany8 sites

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Düsseldorf, 40225

  • Novartis Investigative Site

    Frankfurt/M, 60590

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Leipzig, 04103

  • Novartis Investigative Site

    Mainz, 55131

  • Novartis Investigative Site

    Mannheim, 68169

  • Novartis Investigative Site

    München, 81675

Other trials in Germany

United Kingdom8 sites

  • Novartis Investigative Site

    Birmingham, B15 2TH

  • Novartis Investigative Site

    Cambridge, CB2 2QQ

  • Novartis Investigative Site

    Glasgow - Scotland, G12 OYN

  • Novartis Investigative Site

    Leeds, LS9 7TF

  • Novartis Investigative Site

    Liverpool, L7 8XP

  • Novartis Investigative Site

    London, SE5 9RS

  • Novartis Investigative Site

    London, W12 0NN

  • Novartis Investigative Site

    Newcastle upon Tyne, NE1 4LP

Other trials in United Kingdom

Poland5 sites

  • Novartis Investigative Site

    Katowice, 40-635

  • Novartis Investigative Site

    Lodz, 90-153

  • Novartis Investigative Site

    Warsaw, 02-097

  • Novartis Investigative Site

    Warsaw, 02-776

  • Novartis Investigative Site

    Wroclaw, 50-367

Other trials in Poland

Belgium4 sites

  • Novartis Investigative Site

    Brussels, 1000

  • Novartis Investigative Site

    Haine-Saint-Paul, 7100

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Yvoir, 5530

Other trials in Belgium

Canada4 sites

  • Novartis Investigative Site

    Montreal, Quebec, H1T 2M4

  • Novartis Investigative Site

    Montreal, Quebec, H3A 1A1

  • Novartis Investigative Site

    Toronto, Ontario, M5G 2M9

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 4E3

Other trials in Canada

South Korea4 sites

  • Novartis Investigative Site

    Hwasun-gun, Jeollanam-do, 519-809

  • Novartis Investigative Site

    Seoul, Korea, 05505

  • Novartis Investigative Site

    Seoul, Korea, 137-701

  • Novartis Investigative Site

    Taegu, 700 - 721

Other trials in South Korea

Sweden4 sites

  • Novartis Investigative Site

    Gothenburg, SE-413 45

  • Novartis Investigative Site

    Linköping, SE-581 85

  • Novartis Investigative Site

    Lund, SE-221 85

  • Novartis Investigative Site

    Uppsala, SE-751 85

Other trials in Sweden

Australia3 sites

  • Novartis Investigative Site

    Adelaide, South Australia, 5000

  • Novartis Investigative Site

    Prahran, Victoria, 3181

  • Novartis Investigative Site

    St Leonards, New South Wales, 2065

Other trials in Australia

Netherlands2 sites

  • Novartis Investigative Site

    Amsterdam, 1081 HV

  • Novartis Investigative Site

    Rotterdam

Other trials in Netherlands

Spain2 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08036

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Catalonia, 08907

Other trials in Spain

Switzerland2 sites

  • Novartis Investigative Site

    Basel, 4031

  • Novartis Investigative Site

    Geneva, 1211

Other trials in Switzerland

Austria1 site

  • Novartis Investigative Site

    Vienna, A-1090

Other trials in Austria

Denmark1 site

  • Novartis Investigative Site

    Vejle, DK-7100

Other trials in Denmark

Finland1 site

  • Novartis Investigative Site

    HUS Helsinki, FIN-00029

Other trials in Finland

Hong Kong1 site

  • Novartis Investigative Site

    Pokfulam, Hong Kong

Other trials in Hong Kong

New Zealand1 site

  • Novartis Investigative Site

    Grafton, Auckland

Other trials in New Zealand

Norway1 site

  • Novartis Investigative Site

    Oslo, NO-0310

Other trials in Norway

Singapore1 site

  • Novartis Investigative Site

    Singapore, 169608

Other trials in Singapore

Taiwan1 site

  • Novartis Investigative Site

    Niaosong Township, Taiwan, 83301

Other trials in Taiwan

About this study

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.

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)

Read more

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)

Being tested
Nilotinib
Keywords
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
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Hypereosinophilic Syndrome, Mastocytosis, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NilotinibDrug

Study groups in NCT00109707
Study groupRoleWhat they receive
CML-CP With Prior Imatinib OnlyExperimentalImatinib-resistant / intolerant PH+ CML-CP patients
Receives: Drug: Nilotinib
CML-AP With Prior Imatinib OnlExperimentalImatinib-resistant / intolerant PH+ CML-AP patients
Receives: Drug: Nilotinib
CML-CPExperimentalImatinib-resistant / intolerant PH+ CML-CP patients
Receives: Drug: Nilotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Major Cytogenetic Response (MCyR)

    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).

    Measured: Up to End of the Treatment (Approximately 7.5 years)

  2. Number of Participants Confirmed Overall Hematological Response (Phase II)

    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.

    Measured: Up to End of the Treatment (Approximately 7.5 years)

Secondary outcomes (6)

  1. Number of Participants With Overall Major Cytogenetic Responses (Phase II)

    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).

    Measured: Up to End of the Treatment (Approximately 7.5 years)

  2. Number of Participants With Complete Hematologic Response (Phase II)

    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.

    Measured: Up to End of the Treatment (Approximately 7.5 years)

  3. Participants With (MMR) Major Molecular Response (Phase II)

    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.

    Measured: Up to End of the Treatment (Approximately 7.5 years)

  4. Time to Progression (TTP) (Phase II)

    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).

    Measured: Up to End of the Treatment (Approximately 7.5 years)

  5. Overall Survival (OS) (Phase II)

    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.

    Measured: Up to End of the Treatment (Approximately 7.5 years)

  6. Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety

    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.

    Measured: From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2005 (estimated)
  2. Study startApr 2005
  3. Primary completionSep 2012
  4. Study completionSep 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
507 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00109707
Sponsor's protocol ID
CAMN107A2101
Status last verified
Jun 2021
First submitted
2 May 2005
Last updated
29 Jun 2021

Publications

  • Hochhaus A, Baccarani M, Giles FJ, le Coutre PD, Muller MC, Reiter A, Santanastasio H, Leung M, Novick S, Kantarjian HM. Nilotinib in patients with systemic mastocytosis: analysis of the phase 2, open-label, single-arm nilotinib registration study. J Cancer Res Clin Oncol. 2015 Nov;141(11):2047-60. doi: 10.1007/s00432-015-1988-0. Epub 2015 May 23.

    PubMed 26002753

  • Hochhaus A, le Coutre PD, Kantarjian HM, Baccarani M, Erben P, Reiter A, McCulloch T, Fan X, Novick S, Giles FJ. Effect of the tyrosine kinase inhibitor nilotinib in patients with hypereosinophilic syndrome/chronic eosinophilic leukemia: analysis of the phase 2, open-label, single-arm A2101 study. J Cancer Res Clin Oncol. 2013 Dec;139(12):1985-93. doi: 10.1007/s00432-013-1529-7. Epub 2013 Sep 22.

    PubMed 24057647

  • Stein AM, Martinelli G, Hughes TP, Muller MC, Beppu L, Gottardi E, Branford S, Soverini S, Woodman RC, Hochhaus A, Kim DW, Saglio G, Radich JP. Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia. BMC Cancer. 2013 Apr 2;13:173. doi: 10.1186/1471-2407-13-173.

    PubMed 23547655

  • Kantarjian HM, Giles FJ, Bhalla KN, Pinilla-Ibarz J, Larson RA, Gattermann N, Ottmann OG, Hochhaus A, Radich JP, Saglio G, Hughes TP, Martinelli G, Kim DW, Shou Y, Gallagher NJ, Blakesley R, Baccarani M, Cortes J, le Coutre PD. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood. 2011 Jan 27;117(4):1141-5. doi: 10.1182/blood-2010-03-277152. Epub 2010 Nov 22.

    PubMed 21098399

  • Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, Ossenkoppele GJ, Nicolini FE, O'Brien SG, Litzow M, Bhatia R, Cervantes F, Haque A, Shou Y, Resta DJ, Weitzman A, Hochhaus A, le Coutre P. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007 Nov 15;110(10):3540-6. doi: 10.1182/blood-2007-03-080689. Epub 2007 Aug 22.

    PubMed 17715389

  • Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006 Jun 15;354(24):2542-51. doi: 10.1056/NEJMoa055104.

    PubMed 16775235

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nilotinib in people with Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive), run by Novartis Pharmaceuticals at 101 sites in 22 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 101 sites in United States, Italy, France, Germany, United Kingdom and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Major Cytogenetic Response (MCyR) (time frame: Up to End of the Treatment (Approximately 7.5 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00109707, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2021.

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