Skip to main content

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

Tennessee

Memphis
Saint Jude Children's Research Hospital
Status: ACTIVE
Contact: Sima C. Jeha
Phone: 901-595-3901

PRIMARY OBJECTIVES:

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 Phase Phase II

Trial Type Treatment

Lead Organization
Saint Jude Children's Research Hospital

Principal Investigator
Sima C. Jeha

  • Primary ID INOMRD
  • Secondary IDs NCI-2019-01062
  • Clinicaltrials.gov ID NCT03913559