Last updated on July 2018

A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL


Brief description of study

The design of a phase I, open label, dose finding study was chosen in order to establish a safe and tolerated dose of single agent ABL001 in CML and Ph+ ALL patients who are relapsed or refractory to or are intolerant of TKIs, and of ABL001+Nilotinib, ABL001+Imatinib and ABL001+Dasatinib in Ph positive CML patients who are relapsed or refractory to TKIs.

Detailed Study Description

This first-in-human trial with ABL001 is a dose escalation study whose primary purpose is to estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of single agent ABL001 in CML or Ph+ ALL patients, and in combination with either Nilotinib or Imatinib or Dasatinib in Ph positive CML patients. The safety, tolerability and pharmacokinetic (PK) profile of ABL001 and ABL001+Nilotinib, ABL001+Imatinib and ABL001+Dasatinib will be assessed together with an evaluation of pharmacodynamic (PD) changes in peripheral blood mononuclear cells (PBMC) and bone marrow aspirates and all data may contribute to the assessment of the RDE.

An understanding of the MTD/RDE, safety profile, PK/PD relationship, and preliminary evidence of anti-CML and ALL activity will be 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 may be intolerant of therapy with TKIs or may develop mutations that promote resistance to TKI therapy. In these patients, ABL001 may provide a novel therapeutic option.

Clinical Study Identifier: NCT02081378

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Daniel J. DeAngelo

Dana Farber Cancer Institute Hematology / Oncology
Boston, MA United States
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Moshe Talpaz

University of Michigan Comprehensive Cancer Center SC
Ann Arbor, MI United States
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Michael J. Mauro

Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering
New York, NY United States
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Jorge E. Cortes

University of Texas/MD Anderson Cancer Center UT MD Anderson
Houston, TX United States
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Novartis Pharmaceuticals

Novartis Investigative Site
Adelaide, Australia
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Novartis Pharmaceuticals

Novartis Investigative Site
Paris Cedex 10, France
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Novartis Pharmaceuticals

Novartis Investigative Site
Bordeaux, France
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Novartis Pharmaceuticals

Novartis Investigative Site
Berlin, Germany
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Novartis Pharmaceuticals

Novartis Investigative Site
Frankfurt, Germany
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Novartis Pharmaceuticals

Novartis Investigative Site
Jena, Germany
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Novartis Pharmaceuticals

Novartis Investigative Site
Roma, Italy
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Novartis Pharmaceuticals

Novartis Investigative Site
Seoul, Korea, Republic of
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Novartis Pharmaceuticals

Novartis Investigative Site
Amsterdam, Netherlands
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Novartis Pharmaceuticals

Novartis Investigative Site
Singapore, Singapore
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Novartis Pharmaceuticals

Novartis Investigative Site
Madrid, Spain
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Michael J. Heinrich

Oregon Health and Science University SC-6
Portland, OR United States
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Michael W. Deininger

Huntsman Cancer Institute SC
Salt Lake City, UT United States
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Novartis Pharmaceuticals

Novartis Investigative Site
Kobe-shi, Japan
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