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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00109707
Ethics application status
Date submitted
2/05/2005
Date registered
3/05/2005
Date last updated
29/04/2016

Titles & IDs
Public title
A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Blood Related Cancers
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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
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
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Skin 0 0 0 0
Other skin conditions
Blood 0 0 0 0
Other blood disorders
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nilotinib

Experimental: Arm 1 - Relapsed / refractory Ph+ ALL patients

Experimental: Arm 2 - Group A and Group B - Imatinib-resistant / intolerant Ph+ CML-BC patients

Experimental: Arm 3 - Group A and Group - Imatinib-resistant / intolerant Ph+ CML-AP patients

Experimental: Arm 4 - Group A and Group B - Imatinib-resistant / intolerant Ph+ CML-CP patients

Experimental: Arm 5 - Hypereosinophilic syndrome and chronic eosinophilic leukemia patients

Experimental: Arm 6 - Systemic Mastocytosis patients


Treatment: Drugs: Nilotinib


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
• 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)
Timepoint [1] 0 0
study duration
Primary outcome [2] 0 0
• To characterize the pharmacokinetic profile of AMN107 in serum and, where samples are available, in tumor cells and normal hematopoietic cells. (phase l)
Timepoint [2] 0 0
duration of study
Primary outcome [3] 0 0
• 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)
Timepoint [3] 0 0
duration of study
Primary outcome [4] 0 0
• To evaluate safety and preliminary anticancer activity of AMN107 in relapsed/refractory patients with Ph+ ALL, HES/CEL and SM. (phase ll)
Timepoint [4] 0 0
duration of study
Secondary outcome [1] 0 0
To assess changes during and after therapy in malignant cells taken from the bone marrow and/or blood.(phase ll)
Timepoint [1] 0 0
study duration
Secondary outcome [2] 0 0
To evaluate the population pharmacokinetics of AMN107 (all arms of the study) (phase ll)
Timepoint [2] 0 0
study duration
Secondary outcome [3] 0 0
To examine whether individual genetic variation in genes relating to drug metabolism, CML and the drug pathway confer differential response to AMN107 (phase ll)
Timepoint [3] 0 0
study duration
Secondary outcome [4] 0 0
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)
Timepoint [4] 0 0
study duration

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
Gender
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/Phase 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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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Colorado
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Florida
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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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United States of America
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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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United States of America
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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
State/province [23] 0 0
British Columbia
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Canada
State/province [24] 0 0
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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Duesseldorf
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Frankfurt/M
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Hamburg
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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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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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Warszawa
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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
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Niaosong Township
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United Kingdom
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Birmingham
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Cambridge
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United Kingdom
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Glasgow - Scotland
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Leeds
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Liverpool
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London
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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/show/NCT00109707
Trial related presentations / publications
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
Other publications