M16-106 adult and pediatric ALL clinical trial - RNAseq dataset

Combining venetoclax, a selective BCL-2 inhibitor, with low-dose navitoclax, a BCL-XL/BCL-2 inhibitor, may potentiate therapeutic BCL-2 and BCL XL inhibition without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase 1 dose escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase 2 dose of 50 mg navitoclax for adults and 25 mg for patients <45 kg with 400 mg adult-equivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen (28%) patients proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population. Overall design: The M16-106 trial tested Venetoclax in combination with Navitoclax in adult and pediatric patients with relapsed/refractory ALL. Tumor samples were collected at baseline, total stranded transcriptome sequencing was performed using the TruSeq Stranded Total RNA library preparation kit and sequencing performed using HiSeq 4000 and NovaSeq 6000 platforms (Illumina). The low input RNA library preparation kit (NuGen Ovation V2) was used for samples with limiting material.