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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02081378




Registration number
NCT02081378
Ethics application status
Date submitted
28/02/2014
Date registered
7/03/2014

Titles & IDs
Public title
A Phase I Study of Oral Asciminib (ABL001) in Patients With CML or Ph+ ALL
Scientific title
A Phase I, Multicenter, Open-label Study of Oral ABL001 in Patients With Chronic Myelogenous Leukemia (CML) or Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Secondary ID [1] 0 0
2013-004491-36
Secondary ID [2] 0 0
CABL001X2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myelogenous Leukemia 0 0
Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia 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
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
Treatment: Drugs - Asciminib (ABL001)
Treatment: Drugs - Nilotinib
Treatment: Drugs - Imatinib
Treatment: Drugs - Dasatinib

Experimental: Asciminib in CML patients - Dose escalation study estimated the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of asciminib in adult patients with chronic myeloid leukemia (CML).

Experimental: Asciminib+Nilotinib in CML patients - Dose escalation study estimated the MTD and/or RDE of asciminib in combination with Nilotinib in adult CML patients

Experimental: Asciminib in Ph+ ALL patients - Dose escalation study estimated the MTD and/or RDE of asciminib in adult patients with Ph positive ALL patients

Experimental: Asciminib+Imatinib in CML patients - Dose escalation study to estimate the MTD and/or RDE of asciminib in combination with imatinib in adult CML patients

Experimental: Asciminib+dasatinib in CML patients - Dose escalation study estimated the MTD and/or RDE of asciminib in combination with dasatinib in adult CML patients


Treatment: Drugs: Asciminib (ABL001)
Asciminib was be administered orally in a dose escalation schedule.

Treatment: Drugs: Nilotinib
Asciminib and Nilotinib was administered orally in CML patients

Treatment: Drugs: Imatinib
Asciminib and imatinib was administered orally in CML patients

Treatment: Drugs: Dasatinib
Asciminib and dasatinib was administered orally in CML patients
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLTs) during the first cycle of study treatment
Timepoint [1] 0 0
First Cycle is 28 days
Secondary outcome [1] 0 0
Hematologic Response
Timepoint [1] 0 0
At screening and first day of cycle 2 and 3 and every 12 weeks afterwards
Secondary outcome [2] 0 0
Cytogenetic response
Timepoint [2] 0 0
at screening or when a patient's BCR-ABL ratio has risen to >1%
Secondary outcome [3] 0 0
BCR-ABL transcript level
Timepoint [3] 0 0
At screening and first day of cycle 2 and 3 and every 12 weeks afterwards
Secondary outcome [4] 0 0
Cmax of ABL001 as measured in plasma
Timepoint [4] 0 0
Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.
Secondary outcome [5] 0 0
Cmin of ABL001 as measured in plasma
Timepoint [5] 0 0
Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.
Secondary outcome [6] 0 0
AUCinf of ABL001 as measured in plasma
Timepoint [6] 0 0
Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.
Secondary outcome [7] 0 0
AUClast of ABL001 as measured in plasma
Timepoint [7] 0 0
Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.
Secondary outcome [8] 0 0
AUCtau of ABL001 as measured in plasma
Timepoint [8] 0 0
Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.
Secondary outcome [9] 0 0
T1/2 of ABL001 as measured in plasma
Timepoint [9] 0 0
Cycle 1 days 1,2,8,15,16 and 22. Cycle 2 days 1 and 2, and subsequent cycles at the begining of each cycle up to cycle 6.
Secondary outcome [10] 0 0
Adverse events
Timepoint [10] 0 0
Collected from screening visit through post-treatment follow-up period

Eligibility
Key inclusion criteria
For CML patients either:

* a. Patients with Ph+ CML in chronic or accelerated phase who were previously treated with at least two different tyrosine kinase inhibitors prior to study entry and are relapsed, refractory to or intolerant of TKIs as determined by investigators or
* b. Patients with CML in chronic or accelerated phase who exhibit relapsed disease associated with the presence of the T315I "gatekeeper mutation" after at least one TKI are also eligible provided that no other effective therapy exists

For ALL and CML-BP patients:

* Patients with CML BP or Ph+ ALL who have a cytopathologically confirmed diagnosis and are relapsed or refractory to at least one prior TKI or intolerant of TKIs. TKI failure for Ph+ ALL and CML-BP patients is defined as at least the loss of Molecular Response (MR) 4.5 (BCR-ABL = 0.0032%)
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
* Willingness and ability to comply with all study procedures
* Written informed consent obtained prior to any screening procedures
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Wash-out period:

* Systemic antineoplastic therapy (including cytotoxic chemotherapy, alfa-interferon and toxin immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is shorter, before the first dose of study treatment
* Therapy with TKIs as single agent within 5 half-lives before the first dose of study treatment
* Unconjugated monoclonal antibody therapies within 28 days or 5 half-lives, whichever is shorter, before the first dose of study treatment
* For patients receiving ABL001 in combination with either nilotinib or imatinib or dasatinib, intolerance to nilotinib, imatinib or dasatinib, respectively
* Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment.
* CNS irradiation for meningeal leukemia, except if radiotherapy occurred > 3 months previously. At least four weeks must have elapsed since prophylactic CNS irradiation given as part of a front-line therapy regimen for ALL
* Major surgery within 2 weeks before the first dose of study treatment

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
Single group
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
24/04/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/03/2023
Sample size
Target
Accrual to date
Final
326
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
France
State/province [7] 0 0
Cedex 10
Country [8] 0 0
France
State/province [8] 0 0
Bordeaux
Country [9] 0 0
Germany
State/province [9] 0 0
Berlin
Country [10] 0 0
Germany
State/province [10] 0 0
Frankfurt
Country [11] 0 0
Germany
State/province [11] 0 0
Jena
Country [12] 0 0
Italy
State/province [12] 0 0
RM
Country [13] 0 0
Japan
State/province [13] 0 0
Hyogo
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seocho Gu
Country [15] 0 0
Netherlands
State/province [15] 0 0
Amsterdam
Country [16] 0 0
Singapore
State/province [16] 0 0
Singapore
Country [17] 0 0
Spain
State/province [17] 0 0
Madrid

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02081378