A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- 70
Summary
- Conditions
- Chronic Myelogenous Leukemia
- Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
- Type
- Interventional
- Phase
- Phase 1
- Design
- Allocation: Non-RandomizedIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
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 P...
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.
Tracking Information
- NCT #
- NCT02081378
- Collaborators
- Not Provided
- Investigators
- Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals