Relapsed/refractory acute lymphoblastic leukemia remains a challenge in the context of limited access to immunotherapy in developing countries. With such poor 5-year overall survival rates of 10%, the investigators need strategies that surpass the complete response rate achieved in this setting, which does not exceed 60% effectiveness with different regimens, and to eventually transfer patients to hematopoietic stem cell transplantation.
In this context, the investigators are studyng if the use of venetoclax, a BCL2 inhibitor, with the use of a cytochrome p450 inhibitor such as itraconazole, alongside the TACL chemotherapy regimen, which is based on the combination of asparaginase, dexamethasone, bortezomib, vincristine, and mitoxantrone.
B-cell or T-cell acute lymphoblastic leukemia.
Philadelphia chromosome negative
Relapsed disease after any line of treatment, defined as detection of disease activity at any time after remission
Refractory disease after first-line treatment, defined as: more than 5% blasts after completion of induction/consolidation by flow cytometry
Isolated CNS relapse.
Performance status defined by ECOG scale between 3 and 4.
CTCAE-classified sensory or motor neuropathy of grade 3 or higher.
History of hypersensitivity or intolerance to the drugs included in the regimen.
Single group
Venetoclax low dose with itraconazole
DrugThe investigators will add venetoclax in low dose (100 mg) with itraconazole to the pediatric inspired regimen TACL to enchance the complete response rate
Overall response rata after low dose venetoclax with itraconazole plus TACL
To evaluate the overall response after reinduction to remission with low dose venetoclax plus TACL in patients with relapsed/refractory acute lymphoblastic leukemia
Percentage of measurable residual disease in complete response
Describe the percentage of residual measurable disease in patients with complete response or complete response with incomplete hematologic recovery
Adverse events evaluatio
Identify the most frequent adverse events following the administration of venetoclax + TACL according to the CTCAE version 5 criteria
Patients recieving HSCT after chemotherapy
Determinate the percentage of patients who receive hematopoietic stem cell transplant after treatment with low dose venetoclax with itraconazole plus TACL
Event-free survival
Evaluate event-free survival following low dose venetoclax with itraconazole plus TACL regimen
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