B cell acute lymphoblastic leukemia (B-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of B-lineage precursor cells. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curable therapy for ALL, especially for high-risk ALL patients. However, post-HSCT recurrence is the primary cause of transplant failure and salvage treatment option for this patient population are very limited. Current data showed that the CR rate and overall survival (OS) in adults with ALL who relapse after transplantation are as low as 30% and 25%, respectively, and the prognosis is extremely dismal. Some researchers have successfully salvage treated relapsed B-ALL patients after transplantation with donor lymphocyte infusions (DLI), but the response rate of DLI alone is usually less than 10%, with increased risk of Graft-Versus-Host Disease (GvHD). In the immunotherapy era, the introduction of immuno-designed therapies like bispecific antibody constructs, antibody conjugates, as well as chimeric antigen receptor T cell (CAR-T) therapy, have immensely broadened the treatment landscape of relapsed or refractory (r/r) B-ALL. Inotuzumab ozogamicin (InO) is a CD22-targeted monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. Based on the pivotal Phase III INO-VATE clinical trial published in N Engl J Med in 2016, compared to standard chemotherapy, 73% (64/88) of r/r B-ALL patients treated with InO achieved CR/CRi in the first cycle. Superior CR duration, OS and relapse free survival (RFS) was also observed in the InO group. Subgroup analysis showed that the treatment benefits were consistent for patients who relapsed after allo-HSCT. Moreover, a single-center retrospective study attempted to salvage treat relapsed B-ALL patients after transplantation with combined InO and DLI, results showed that six out of eight patients achieved CR after the first InO course and 75% of patients obtained MRD negativity after the second course, which is quite satisfactory. Therefore, we designed a Phase II clinical study of InO combined with or without DLI in patients with recurrent acute B-ALL/LBL after allo-HSCT, with expectation to increase CR rate and improve long-term survival.
Aged 14-65 years, male or female;
Participants with CD22 positive B-ALL/LBL who relapsed after allo-HSCT from a related or unrelated donor (regardless of CD22 expression);
ECOG physical status score 0~3, Karnofsky score ≥70;
No active grade III/IV graft-versus-host disease (GvHD) or any active liver GvHD, no history of venous occlusive disease (VOD); No active GvHD and no previous history of VOD;
Allergic or with a history of serious adverse reactions to drugs or drugs with similar chemical structure in this study;
Women who are pregnant or breastfeeding, as well as those who are unwilling to take effective contraceptive measures;
Severe cardiac dysfunction: left ventricular ejection fraction (LVEF) <60%; Or severe arrhythmia: a history of a clinically significant corrected interval (QTc) prolongation (male >450ms; female>470 ms), ventricular tachycardia, atrial fibrillation, second degree atrioventricular block; myocardial infarction and coronary heart disease with clinical symptoms requiring medical treatment within one year before enrollment;
Severe pulmonary disorders (obstructive or restrictive ventilation disorder);