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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00109707




Registration number
NCT00109707
Ethics application status
Date submitted
2/05/2005
Date registered
3/05/2005
Date last updated
29/06/2021

Titles & IDs
Public title
A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies
Scientific 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.
Secondary ID [1] 0 0
CAMN107A2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myelogenous Leukemia 0 0
Acute Lymphoblastic Leukemia (Philadelphia Chromosome Positive) 0 0
Hypereosinophilic Syndrome 0 0
Systemic Mastocytosis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Skin 0 0 0 0
Other skin conditions
Blood 0 0 0 0
Other blood disorders
Blood 0 0 0 0
Haematological diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: CML-CP With Prior Imatinib Only - Imatinib-resistant / intolerant PH+ CML-CP patients

Experimental: CML-AP With Prior Imatinib Onl - Imatinib-resistant / intolerant PH+ CML-AP patients

Experimental: CML-CP - Imatinib-resistant / intolerant PH+ CML-CP patients
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Major Cytogenetic Response (MCyR)
Timepoint [1] 0 0
Up to End of the Treatment (Approximately 7.5 years)
Primary outcome [2] 0 0
Number of Participants Confirmed Overall Hematological Response (Phase II)
Timepoint [2] 0 0
Up to End of the Treatment (Approximately 7.5 years)
Secondary outcome [1] 0 0
Number of Participants With Overall Major Cytogenetic Responses (Phase II)
Timepoint [1] 0 0
Up to End of the Treatment (Approximately 7.5 years)
Secondary outcome [2] 0 0
Number of Participants With Complete Hematologic Response (Phase II)
Timepoint [2] 0 0
Up to End of the Treatment (Approximately 7.5 years)
Secondary outcome [3] 0 0
Participants With (MMR) Major Molecular Response (Phase II)
Timepoint [3] 0 0
Up to End of the Treatment (Approximately 7.5 years)
Secondary outcome [4] 0 0
Time to Progression (TTP) (Phase II)
Timepoint [4] 0 0
Up to End of the Treatment (Approximately 7.5 years)
Secondary outcome [5] 0 0
Overall Survival (OS) (Phase II)
Timepoint [5] 0 0
Up to End of the Treatment (Approximately 7.5 years)
Secondary outcome [6] 0 0
Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety
Timepoint [6] 0 0
From First Participant First Visit to Last Participant Last Visit (Approximately 7.5 years)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2012
Sample size
Target
Accrual to date
Final
507
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - St. Leonards
Recruitment hospital [2] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [3] 0 0
Novartis Investigative Site - Prahran
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Colorado
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United States of America
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Florida
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United States of America
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Illinois
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Indiana
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United States of America
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Louisiana
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United States of America
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Maryland
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Massachusetts
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Michigan
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Minnesota
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New Jersey
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New York
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North Carolina
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Oregon
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Tennessee
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Texas
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Washington
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Austria
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Wien
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Belgium
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Bruxelles
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Belgium
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Haine-saint-Paul
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Belgium
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Leuven
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Belgium
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Yvoir
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Denmark
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Vejle
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Finland
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HUS Helsinki
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France
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Bordeaux Cedex
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France
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Créteil
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France
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Dijon
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France
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Lille
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France
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Limoges cedex
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France
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Lyon
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France
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Marseille
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France
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Poitiers
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France
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Rennes
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France
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Vandoeuvre les Nancy
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Germany
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Berlin
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Germany
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Duesseldorf
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Germany
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Frankfurt/M
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Germany
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Hamburg
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Germany
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Leipzig
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Germany
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Mainz
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Germany
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Mannheim
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Germany
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Muenchen
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Hong Kong
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Pokfulam
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Italy
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BG
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Italy
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BO
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Italy
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GE
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Italy
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MB
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Italy
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MI
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Italy
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PE
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Italy
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PV
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Italy
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RC
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Italy
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RM
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Italy
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TO
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Italy
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Napoli
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Korea, Republic of
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Jeollanam-do
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Korea, Republic of
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Korea
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Korea, Republic of
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Taegu
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Netherlands
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Amsterdam
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Netherlands
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Rotterdam
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New Zealand
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Auckland
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Norway
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Oslo
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Poland
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Katowice
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Poland
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Lodz
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Poland
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Warszawa
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Poland
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Wroclaw
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Singapore
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Singapore
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Spain
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Catalunya
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Sweden
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Göteborg
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Sweden
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Linköping
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Sweden
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Lund
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Sweden
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Uppsala
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Switzerland
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Basel
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Switzerland
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Genève
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Taiwan
State/province [77] 0 0
Niaosong Township
Country [78] 0 0
United Kingdom
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Birmingham
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United Kingdom
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Cambridge
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United Kingdom
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Glasgow - Scotland
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United Kingdom
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Leeds
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United Kingdom
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Liverpool
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United Kingdom
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London
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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)
Trial website
https://clinicaltrials.gov/study/NCT00109707
Trial related presentations / 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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticlas
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00109707