A single arm, phase II study to evaluate the efficacy of oral maintenance therapy with 6 mercaptopurine and methotrexate in patients of relapsed/refractory (R/R)-B ALL with early loss of B-cell aplasia post CAR-T infusion.

When it comes to relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), CAR-T cell therapy has greatly improved outcomes. However, due in significant part to the short durability of CAR-T cells, over 50% of patients relapse within 1-2 years. A significant risk of relapse is linked to early loss of B-cell aplasia, which is a surrogate indicator of poor CAR-T persistence.Such high-risk patients have few management alternatives. While hematopoietic stem cell transplantation (HSCT) is successful, it is frequently not practical due to patient frailty, donor availability, and expensive cost, especially in the Indian environment. Repeat CAR-T infusion involves severe toxicity and dubious long-term benefit. The purpose of this trial is to determine whether low-dose oral maintenance chemotherapy can increase survival and decrease relapse in B-ALL patients treated with CAR-T who exhibit early B-cell depletion.

This study aims to evaluate whether low-dose oral maintenance chemotherapy can reduce relapse and improve survival in CAR-T–treated B-ALL patients who demonstrate early loss of B-cell aplasia and are ineligible for second CAR-T infusion or HSCT. The maintenance regimen includes oral 6-mercaptopurine and methotrexate, based on their immunomodulatory role in standard B-ALL therapy.The primary objective is to assess 1-year event-free survival. Secondary objectives include evaluating the efficacy of maintenance chemotherapy in preventing relapse and improving overall outcomes in this high-risk population.