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

• Status: Active, not recruiting
• Trial end date: 2024-03-14
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Dasatinib; Imatinib Mesylate; Niacinamide

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