Clinical Trials /

Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia

NCT03913559

Description:

This trial is a limited multi-center, Phase II study to evaluate inotuzumab ozogamicin (Besponsa) in pediatric patients with MRD positive CD22-positive B-lymphoblastic leukemia (B-ALL). Some patients with newly diagnosed ALL maintain low levels of MRD, despite achieving complete remission with less than 5% blasts in the bone marrow. Others experience re-emergence of low level MRD or increasing levels of MRD on therapy or post-transplant. New approaches are needed to achieve undetectable MRD in these high-risk patients. Inotuzumab ozogamicin is an antibody-drug conjugate composed of a humanized IgG subtype 4 monoclonal CD22-targeted antibody linked to calicheamicin, a potent anti-tumor antibiotic. CD22 is expressed in more than 90% of patients with B-cell ALL, making it an attractive target in this patient population. Inotuzumab ozogamicin has demonstrated exceptional activity in adults with relapsed or refractory B-ALL. Primary Objective Assess the effectiveness of inotuzumab ozogamicin in patients with MRD positive CD22+ B-ALL Secondary Objectives - Study the safety of inotuzumab ozogamicin when used in patients with MRD - positive CD22+ B-ALL with < 5 % blasts in bone marrow. - 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).

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia
  • Official Title: Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: INOMRD
  • SECONDARY ID: NCI-2019-01062
  • NCT ID: NCT03913559

Conditions

  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
Inotuzumab ozogamicinBesponsaInotuzumab ozogamicin
MethotrexateTrexallInotuzumab ozogamicin
HydrocortisoneCortisolInotuzumab ozogamicin
CytarabineAra-CInotuzumab ozogamicin
DiphenhydramineBenadrylInotuzumab ozogamicin
AcetaminophenTylenolInotuzumab ozogamicin
MethylprednisoloneSolu-MedrolInotuzumab ozogamicin

Purpose

This trial is a limited multi-center, Phase II study to evaluate inotuzumab ozogamicin (Besponsa) in pediatric patients with MRD positive CD22-positive B-lymphoblastic leukemia (B-ALL). Some patients with newly diagnosed ALL maintain low levels of MRD, despite achieving complete remission with less than 5% blasts in the bone marrow. Others experience re-emergence of low level MRD or increasing levels of MRD on therapy or post-transplant. New approaches are needed to achieve undetectable MRD in these high-risk patients. Inotuzumab ozogamicin is an antibody-drug conjugate composed of a humanized IgG subtype 4 monoclonal CD22-targeted antibody linked to calicheamicin, a potent anti-tumor antibiotic. CD22 is expressed in more than 90% of patients with B-cell ALL, making it an attractive target in this patient population. Inotuzumab ozogamicin has demonstrated exceptional activity in adults with relapsed or refractory B-ALL. Primary Objective Assess the effectiveness of inotuzumab ozogamicin in patients with MRD positive CD22+ B-ALL Secondary Objectives - Study the safety of inotuzumab ozogamicin when used in patients with MRD - positive CD22+ B-ALL with < 5 % blasts in bone marrow. - 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).

Detailed Description

      The drug will be administered intravenously on days one, eight and 15 of each 28-day cycle.
      Patients who do not meet the definition of treatment failure after the first cycle may
      receive up to five additional cycles of therapy. .

      After completion of study treatment, patients are followed up for 1 year
    

Trial Arms

NameTypeDescriptionInterventions
Inotuzumab ozogamicinExperimentalExperimental:Inotuzumab Ozogamicin (InO) Patients with B cell acute lymphoblastic leukemia (B-ALL) that is showing early signs of relapsing (coming back) or is not responding to treatment (refractory). Interventions:methotrexate, hydrocortisone and cytarabine into the central nervous system ((called triple intrathecal chemotherapy or IT chemotherapy) during this study. Premedication: diphenhydramine, acetaminophen and methylprednisolone
  • Inotuzumab ozogamicin
  • Methotrexate
  • Hydrocortisone
  • Cytarabine
  • Diphenhydramine
  • Acetaminophen
  • Methylprednisolone

Eligibility Criteria

        Inclusion Criteria:

        Age

        Younger than 22 years old

        Diagnosis

          -  Participants must have B-ALL with persistent or rising MRD between 0.1 and 4.99%
             without extramedullary disease following at least two prior induction attempts,
             relapse or after hematopoietic stem cell transplant

          -  Leukemia blasts demonstrating surface expression of CD22

        Performance Level

          -  Karnofsky or Lansky performance score ≥ 50%

        Exclusion Criteria:

          -  History of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD)

          -  Concurrent chemotherapy or targeted anti-cancer agents, other than intrathecal
             therapy.

          -  Known HIV infection or active hepatitis B or C

          -  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).

          -  Pregnant or breastfeeding
      
Maximum Eligible Age:22 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment response Cycle1 - count
Time Frame:At the end of cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Number of patients that reach MRD negative at the end of cycle 1

Secondary Outcome Measures

Measure:Occurrence of death - count
Time Frame:up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant
Safety Issue:
Description:Number of patient deaths that occur at any time during observation on study
Measure:Occurrence of death - percentage
Time Frame:up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant
Safety Issue:
Description:Percentage of patient deaths that occur at any time during observation on study
Measure:Occurrence of Veno-occlusive disease (VOD) - count
Time Frame:up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant
Safety Issue:
Description:Number of patients that develop VOD at any time during observation on study
Measure:Occurrence of Veno-occlusive disease (VOD) - percentage
Time Frame:up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant
Safety Issue:
Description:Percentage of patients that develop VOD at any time during observation on study

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:St. Jude Children's Research Hospital

Trial Keywords

  • B-cell Acute Lymphoblastic Leukemia

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