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Inotuzumab Ozogamicin in Treating Patients with MRD Positive CD22+ Relapsed B Cell Acute Lymphoblastic Lymphoma
Trial Status: active
This phase II trial studies how well inotuzumab ozogamicin works in treating patients with minimal residual disease (MRD) positive CD22 positive (+) B cell acute lymphoblastic lymphoma that has come back. Minimal residual disease is when there is evidence for remaining tumor following initial treatment that is only apparent using highly sensitive techniques, but there are no other signs of leukemia in the bone marrow or blood yet. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22+ cancer cells in a targeted way and delivers ozogamicin to kill them.
Inclusion Criteria
Participants must have B-ALL with persistent or rising MRD between 0.1 and 4.99% without extramedullary disease following at least 2 prior induction attempts, relapse or after HSCT
Leukemia blasts must demonstrate surface expression of CD22 by local/institutional flow cytometry of a bone marrow aspirate
Karnofsky or Lansky performance score is >= 50% (corresponding to Eastern Cooperative Oncology Group [ECOG] score of >= 2). The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants >= 16 years
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study
At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of standard maintenance therapy and steroids
At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody with the exception of blinatumomab. Patients must have been off blinatumomab infusion for at least 7 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria
At least 42 days must have elapsed since chimeric antigen receptor (CAR)-T cell therapy
Participant has received =< 1 prior bone marrow transplant
At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for >= 2 weeks, if applicable with no evidence of active graft versus host disease (GVHD)
At least 2 weeks must have elapsed since local radiation therapy (XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
Adequate renal function defined as glomerular filtration rate >= 60 cc/min/1.73 m^2 or serum creatinine based on age as follows:
* Age < 6 months: 0.4 mg/dL for males and 0.4 mg/dL for females
* Age 6 months to < 1 year: 0.5 mg/dL for males and 0.5 mg/dL for females
* Age 1 to < 2 years: 0.6 mg/dL for males and 0.6 mg/dL for females
* Age 2 to < 6 years: 0.8 mg/dL for males and 0.8 mg/dL for females
* Age 6 to < 10 years: 1 mg/dL for males and 1 mg/dL for females
* Age 10 to < 13 years: 1.2 mg/dL for males and 1.2 mg/dL for females
* Age 13 to < 16 years: 1.5 mg/dL for males and 1.4 mg/dL for females
* Age >= 16 years: 1.7 mg/dL for males and 1.4 mg/dL for females
Direct bilirubin =< 1.4 mg/dL (if total bilirubin > 1.4 mg/dL)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) for age
Adequate cardiac function defined as shortening fraction of >= 27% or ejection fraction >= 45%
Exclusion Criteria
Patients with any history of sinusoidal obstructive syndrome/veno-occlusive disease (SOS/VOD) of any severity
Concurrent chemotherapy or targeted anti-cancer agents, other than intrathecal therapy
Patient with concurrent severe and/or uncontrolled medical conditions that, in the opinion of the investigator, may impair participation in the study or the evaluation of safety and/or efficacy
Known human immunodeficiency virus (HIV) infection or active hepatitis B (defined as hepatitis B surface antigen–positive) or C (defined as hepatitis C antibody–positive)
Pregnant or lactating (female participant of childbearing potential must have negative serum or urine pregnancy test required within 7 days prior to start of treatment)
Male or female participant of reproductive potential must agree to use appropriate methods of contraception for the duration of study treatment and for at least 30 days after last dose of protocol treatment
Inability or unwillingness or research participant or legal guardian/representative to give written informed consent
Additional locations may be listed on ClinicalTrials.gov for NCT03913559.
I. Assess the efficacy of inotuzumab ozogamicin in patients with MRD positive CD22+ B acute lymphoblastic lymphoma (B-ALL) with 0.1 - 4.99% blasts in bone marrow.
SECONDARY OBJECTIVES:
I. Study the safety of inotuzumab ozogamicin when used in patients with MRD positive CD22+ B-ALL with < 5 % blasts in bone marrow.
II. Estimate the incidence, severity, and outcome of hepatotoxicity and sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in patients during inotuzumab ozogamicin and following subsequent treatment, including hematopoietic stem cell transplant (HSCT).
OUTLINE:
Patients receive inotuzumab ozogamicin intravenously (IV) over 60 minutes on days 1, 8, and 15. Patients also receive methotrexate intrathecally (IT), hydrocortisone sodium succinate IT, and cytarabine IT weekly or every 2 weeks. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationSaint Jude Children's Research Hospital