Study of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone for Relapsed B-cell ALL

Required: CD22 surface expression ≥ 20% of leukemic blasts (≥ 20% of leukemic blasts)

At least 20% of leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by flow cytometry of a bone marrow aspirate... Alternatively, CD22 expression may be documented by immunohistochemistry of a relapse bone marrow biopsy specimen.

Must have received: cytotoxic chemotherapy — frontline

Primary refractory disease: defined as > 1% bone marrow blasts by flow MRD after at least 2 courses of frontline chemotherapy. Patients who receive 2 courses of chemotherapy and 1 course of blinatumomab are also eligible, but no further treatment attempts beyond that are permitted.

Must have received: hematopoietic stem cell transplant

Any relapse after HSCT or CAR-T therapy.

Must have received: CAR-T cell therapy

Any relapse after HSCT or CAR-T therapy.

Cannot have received: inotuzumab ozogamicin (inotuzumab ozogamicin)

Exception: ≤ 2.1 mg/m2 prior InO and at least 90 days from last dose

Prior Inotuzumab ozogamicin Patients with prior InO exposure must have received no more than 2.1 mg/m2 of prior InO and be at least 90 days from last dose.

Cannot have received: venetoclax (venetoclax)

Exception: at least 30 days from last dose

Prior Venetoclax exposure • Patients with prior venetoclax exposure are eligible provided they are at least 30 days from last dose.

Cannot have received: antibody-drug conjugate

Exception: at least 21 days from last dose (except blinatumomab: at least 3 days)

At least 21 days must have elapsed from infusion of last dose of antibody. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days.

Cannot have received: cytotoxic chemotherapy

Exception: at least 14 days from completion of systemic cytotoxic therapy that is known to be myelosuppressive (except hydroxyurea for cytoreduction OR conventional maintenance chemotherapy for patients who relapse while on maintenance therapy OR lumbar puncture with intrathecal chemotherapy); corticosteroids, vincristine, 6MP, and/or oral methotrexate must be discontinued at least 24 hours prior to the start of protocol therapy

At least 14 days must have elapsed from the completion of systemic cytotoxic therapy that is known to be myelosuppressive with the exception of hydroxyurea for cytoreduction OR conventional maintenance chemotherapy (i.e., corticosteroids, vincristine, 6MP, and/or oral methotrexate) for patient who relapse while on maintenance therapy OR lumbar puncture with intrathecal chemotherapy. Corticosteroids, vincristine, 6MP, and/or oral methotrexate must be discontinued at least 24 hours prior to the start of protocol therapy.

Cannot have received: radiation therapy

Exception: at least 14 days since local palliative radiotherapy; at least 3 months since cranial/craniospinal, >50% pelvis, or total body irradiation; at least 6 weeks since other substantial bone marrow irradiation

At least 14 days must have elapsed since local palliative radiotherapy. At least 3 months must have elapsed if patient received cranial or craniospinal radiotherapy, if more than 50% of the pelvis was irradiated, or if total body irradiation was received. If other substantial bone marrow irradiation was given, at least 6 weeks must have elapsed.

Cannot have received: hematopoietic stem cell transplant

Exception: at least 90 days since stem cell transplant and at least 30 days from donor lymphocyte infusion; no more than one previous HSCT; no evidence of active GVHD; off all immunosuppressive medications for at least 28 days

At least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patients must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease and must be off all immunosuppressive medications for at least 28 days.

Cannot have received: CAR-T cell therapy

Exception: at least 30 days from last CAR-T cell infusion; must still have CD22 expression on at least 20% of leukemic blasts

At least 30 days must have elapsed from the last CAR-T cell infusion. Patients may have previously received CD19 or CD22 directed CAR-T cell therapy but must still have CD22 expression on at least 20% of leukemic blasts.