EA9152 – A Phase Ib/II Study of Venetoclax (ABT-199) in Combination with Liposomal Vincristine or Vincristine Sulfate in Patients with Relapsed or Refractory T-cell or B-cell Acute Lymphoblastic Leukemia

The study chair for this trial is Neil Palmisiano, MD, MS (Rutgers Cancer Institute of New Jersey). The study co-chair is David Claxton, MD (Penn State Cancer Institute).

Relapsed B-cell or T-cell acute lymphoblastic leukemia (ALL) remains a therapeutic challenge, especially in older or unfit patients who may not be eligible for cellular therapies. Clinical trial EA9152 is investigating the safety and efficacy of venetoclax, a BCL-2 inhibitor, in combination with vincristine sulfate in the relapsed or refractory ALL population. Early clinical experience with venetoclax has demonstrated its efficacy in a variety of hematologic malignancies, some leading to FDA approvals. It remains experimental for ALL. 

The phase 2 part of this trial is currently active. All patients who enroll receive venetoclax and vincristine sulfate for up to 6 weeks. Patients undergo a bone marrow biopsy on day 28, and those whose disease is at least stable receive a second 28-day cycle of the combination therapy.

Patients with progressive disease discontinue treatment. A bone marrow biopsy is performed again at day 56, and patients whose disease is at least stable may remain on combination therapy until disease progression or withdrawal from the trial. At the discretion of the treating physician, a patient in complete remission or complete remission with incomplete hematologic recovery may proceed to hematopoietic stem cell transplantation at any time.

Newly reopened with amendment 11, several significant changes have been implemented:

1. Liposomal vincristine (Marqibo) has been withdrawn from the market, so for the remainder of the trial, vincristine sulfate will be used
2. Vincristine sulfate 1.4 mg/m² (capped at 2 mg) will be given by IV weekly for 4 weeks for the first cycle, then monthly thereafter
3. In cycle 1 and beyond, venetoclax will be given daily
4. Respecting the potential for different toxicity, close monitoring of adverse events in newly enrolled patients will take place

Key eligibility criteria include a diagnosis of relapsed or refractory B-cell or T-cell ALL, including lymphoblastic lymphoma, after at least one line of chemotherapy; an ECOG performance status of 0-2; age ≥ 18; and adequate kidney and liver function. Patients with prior venetoclax exposure for ALL therapy as well as those with high circulating white blood cell count at the time of cycle 1, day 1 are excluded.

Learn more about EA9152 at ecog-acrin.org.