A phase 1 trial of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory B-cell or T-cell acute lymphoblastic leukemia: Results from the ECOG-ACRIN EA9152 protocol.

Introduction: Relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) remains a therapeutic challenge. Preclinical data in both B- and T-ALL suggests synergy of venetoclax (VEN) with vincristine (VCR). We designed a phase I/II trial (EA9152) of the combination of L-VCR and VEN for patients with r/r B-or T-cell ALL or LL. Here, we report the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644).

Methods: In a 3+3 dose escalation design, r/r ALL subjects were given single-agent VEN doses reaching 400, 600, or 800 mg for the three respective dose levels. Weekly L-VCR at 2.25 mg/m IV was started on D15 of cycle 1. The primary phase I objective was to determine the maximum tolerated dose (MTD) of the combination.

Results: Among the 18 patients in phase I, grade ≥ 3 treatment-related adverse events were reported in 89% of treated patients. Two patients (two of three) at dose level 3 experienced dose-limiting toxicities. Therefore, the MTD of the combination was determined to be dose level 2 (VEN 600 mg). Twenty-two percent of evaluable patients ( = 4) achieved a complete response, with two of them showing no evidence of measurable residual disease (MRD).

Conclusion: The combination of VEN and L-VCR was found to be safe for patients with r/r ALL and encouraging preliminary efficacy, including MRD negative responses. With the removal of L-VCR from the US market, the phase 2 portion of this trial is actively enrolling with vincristine sulfate.