A Phase I Study of Oral Asciminib (ABL001) in Patients With CML or Ph+ ALL
NCT ID: NCT02081378
Last Updated: 2024-03-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
326 participants
INTERVENTIONAL
2014-04-24
2023-03-14
Brief Summary
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Detailed Description
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An understanding of the MTD/RDE, safety profile, PK/PD relationship, and preliminary evidence of anti-CML and ALL activity wias used to inform future development in adults with CML and Ph+ ALL. By virtue of its distinct pharmacological profile and by preclinical pharmacological studies demonstrating an additive effect, a combination of ABL001 and a tyrosine-kinase inhibitor (TKI) has the potential to achieve a deeper molecular response in a higher proportion of CML patients as compared to single agent TKI therapy. Such a combination has the added advantage of targeting the ABL kinase domain at two distinct locations, theoretically preventing single point mutation-associated treatment resistance. The prediction is that a nilotinib+ABL001, imatinib+ABL001 and/or dasatinib+ABL001 combination will increase the percentage of patients who achieve a complete molecular response (CMR) and decrease the time to CMR, thereby increasing the possibility of achieving sustained treatment-free remissions in these patients. In addition, some patients could be intolerant of therapy with TKIs or could develop mutations that promote resistance to TKI therapy. In these patients, ABL001 could provide a novel therapeutic option.
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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).
Asciminib (ABL001)
Asciminib was be administered orally in a dose escalation schedule.
Asciminib+Nilotinib in CML patients
Dose escalation study estimated the MTD and/or RDE of asciminib in combination with Nilotinib in adult CML patients
Asciminib (ABL001)
Asciminib was be administered orally in a dose escalation schedule.
Nilotinib
Asciminib and Nilotinib was administered orally in CML patients
Asciminib in Ph+ ALL patients
Dose escalation study estimated the MTD and/or RDE of asciminib in adult patients with Ph positive ALL patients
Asciminib (ABL001)
Asciminib was be administered orally in a dose escalation schedule.
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
Asciminib (ABL001)
Asciminib was be administered orally in a dose escalation schedule.
Imatinib
Asciminib and imatinib was administered orally in CML patients
Asciminib+dasatinib in CML patients
Dose escalation study estimated the MTD and/or RDE of asciminib in combination with dasatinib in adult CML patients
Asciminib (ABL001)
Asciminib was be administered orally in a dose escalation schedule.
Dasatinib
Asciminib and dasatinib was administered orally in CML patients
Interventions
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Asciminib (ABL001)
Asciminib was be administered orally in a dose escalation schedule.
Nilotinib
Asciminib and Nilotinib was administered orally in CML patients
Imatinib
Asciminib and imatinib was administered orally in CML patients
Dasatinib
Asciminib and dasatinib was administered orally in CML patients
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
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Dana Farber Cancer Institute Hematology / Oncology
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center SC
Ann Arbor, Michigan, United States
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering
New York, New York, United States
Oregon Health Sciences University SC-6
Portland, Oregon, United States
University of Texas/MD Anderson Cancer Center UT MD Anderson
Houston, Texas, United States
Huntsman Cancer Institute SC
Salt Lake City, Utah, United States
Novartis Investigative Site
Adelaide, South Australia, Australia
Novartis Investigative Site
Paris, Cedex 10, France
Novartis Investigative Site
Bordeaux, , France
Novartis Investigative Site
Berlin, , Germany
Novartis Investigative Site
Frankfurt, , Germany
Novartis Investigative Site
Jena, , Germany
Novartis Investigative Site
Roma, RM, Italy
Novartis Investigative Site
Kobe, Hyōgo, Japan
Novartis Investigative Site
Amsterdam, , Netherlands
Novartis Investigative Site
Singapore, , Singapore
Novartis Investigative Site
Seoul, Seocho Gu, South Korea
Novartis Investigative Site
Madrid, , Spain
Countries
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References
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Luskin MR, Murakami MA, Keating J, Flamand Y, Winer ES, Garcia JS, Stahl M, Stone RM, Wadleigh M, Jaeckle SL, Hagopian E, Weinstock DM, Liegel J, McMasters M, Wang ES, Stock W, DeAngelo DJ. Asciminib plus dasatinib and prednisone for Philadelphia chromosome-positive acute leukemia. Blood. 2025 Feb 6;145(6):577-589. doi: 10.1182/blood.2024025800.
Li YF, Combes FP, Hoch M, Lorenzo S, Sy SKB, Ho YY. Population Pharmacokinetics of Asciminib in Tyrosine Kinase Inhibitor-Treated Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic and Acute Phases. Clin Pharmacokinet. 2022 Oct;61(10):1393-1403. doi: 10.1007/s40262-022-01148-9. Epub 2022 Jun 28.
Hughes TP, Mauro MJ, Cortes JE, Minami H, Rea D, DeAngelo DJ, Breccia M, Goh YT, Talpaz M, Hochhaus A, le Coutre P, Ottmann O, Heinrich MC, Steegmann JL, Deininger MWN, Janssen JJWM, Mahon FX, Minami Y, Yeung D, Ross DM, Tallman MS, Park JH, Druker BJ, Hynds D, Duan Y, Meille C, Hourcade-Potelleret F, Vanasse KG, Lang F, Kim DW. Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019 Dec 12;381(24):2315-2326. doi: 10.1056/NEJMoa1902328.
Related Links
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Novartis results database
Other Identifiers
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2013-004491-36
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CABL001X2101
Identifier Type: -
Identifier Source: org_study_id
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