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

Trial Status: Active

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.

Inclusion Criteria

  • 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 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 Other protocol-defined inclusion/exclusion criteria may apply


Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Daniel Joseph DeAngelo
Phone: 617-632-3029


Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: ACTIVE
Contact: Julio Garcia-Castro
Phone: 734-232-0759

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE


OHSU Knight Cancer Institute
Status: ACTIVE
Contact: Barbie Jackson
Phone: 503-494-4603


M D Anderson Cancer Center
Status: ACTIVE


Salt Lake City
Huntsman Cancer Institute / University of Utah

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.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Novartis Pharmaceuticals Corporation

  • Primary ID CABL001X2101
  • Secondary IDs NCI-2014-01571
  • ID NCT02081378