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

Inclusion Criteria

• •Diagnosis:
• •\- Patients must have relapsed B-ALL \> 5 % bone marrow blasts with or without extramedullary disease.
• •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. In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be obtained due to patient clinical status, then flow cytometry of peripheral blood specimens may be substituted if the patient has \> 1,000/µL circulating blasts. Alternatively, CD22 expression may be documented by immunohistochemistry of a relapse bone marrow biopsy specimen.
• •Patients with one of the following:
• •* 2nd or greater relapse OR first relapse less than 24 months from diagnosis OR first or greater relapse in patients over 18.
• •* 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.
• •* Any relapse after HSCT or CAR-T therapy.
• •Patients with Ph+ ALL must have had at least two prior therapy attempts and failed all available tyrosine kinase inhibitors.
• •Prior Therapy:
• •\- Cytotoxic chemotherapy:
• •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. If corticosteroids were used to modify immune adverse events of prior therapy rather than as chemotherapy, at least 14 days must have elapsed since the last dose.
• •Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy. For all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency.
• •At least seven days must have elapsed from the administration of anti-cancer agents not known to be myelosuppressive.
• •Anti-cancer agents that are antibodies
• •• 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.
• •Radiation therapy
• •• 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.
• •Hematopoietic stem cell transplant
• •• 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.
• •Chimeric antigen receptor T-cell therapy
• •• 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.
• •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.
• •Prior Venetoclax exposure • Patients with prior venetoclax exposure are eligible provided they are at least 30 days from last dose.
• •Age:
• •\- Patients must be ≥ 1 year and ≤ 39.99 years of age at enrollment.
• •Performance status:
• •\- Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• •Organ function requirements:
• •Adequate Renal Function Defined As:
• •• An estimated GFR of 50 mL/min/1.73m2 as determined by the Levey formula (see appendix C), cystatin C, or radioisotope determination.
• •Adequate Liver Function Defined As:
• •* Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
• •* SGPT (ALT) \< 2.5 x the age-appropriate upper limit of normal (ULN) per local lab (unless elevation is related to leukemia involvement).
• •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.