Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia

NCT03913559

Last updated date
Study Location
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Contact
866-278-5833

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Acute Lymphoblastic Leukemia
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
0-21
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

Age

- Participants must be < 22 years of age.

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% (corresponding to ECOG Score of ≥ 2). The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants ≥ 16 years.

Prior Therapy

- Patients must have fully recovered from the acute toxic effects of all prior anticancer 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 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 GVHD.

- At least 2 weeks must have elapsed since local 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 TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given.

Organ Function Requirements

- Adequate renal function defined as glomerular filtration rate ≥ 60 cc/min/1.73m2 or serum creatinine based on age as follows:

- Age: <6 months; maximum serum creatinine (mg/dL): 0.4 (male, female); Age: 6 months to <1 year; maximum serum creatinine (mg/dL): 0.5 (male, female); Age: 1 to < 2 years; maximum serum creatinine (mg/dL): 0.6 (male, female); Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male, female); Age: 6 to <10 years; maximum serum creatinine (mg/ dL): 1 (male, female); Age: 10 to <13 years; maximum serum creatinine (mg/dL): 1.2 (male, female); Age: 13 to <16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female); Age: ≥ 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female)

- Adequate hepatic function defined as:

- Direct bilirubin ≤ 1.4 mg/dL (if total bilirubin > 1.4 mg/dL) and

- AST or ALT ≤ 3 x ULN for age.

- Adequate cardiac function defined as shortening fraction of ≥ 27% or ejection fraction ≥ 45%.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- History of sinusoidal obstruction 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 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 of research participant or legal guardian/representative to
give written informed consent.

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Advanced Information
Descriptive Information
Brief Title  ICMJE Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia
Official Title  ICMJE Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia
Brief Summary

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 efficacy of inotuzumab ozogamicin in patients with MRD positive CD22+ B-ALL with 0.1 - 4.99% blasts in bone marrow.

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 1, 8, 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 for 1 year.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Drug: Inotuzumab ozogamicin
    dose: 0.5 mg/m2 IV over 60 minutes, days: 1, 8 and 15 every 4 weeks (28 days per cycle) for up to 6 cycles.
    Other Names:
    • Besponsa
    • CMC-544
  • Drug: Methotrexate
    Intrathecal (IT) therapy
    Other Name: Trexall®
  • Drug: Hydrocortisone
    Intrathecal (IT) therapy
    Other Name: Cortisol
  • Drug: Cytarabine
    Intrathecal (IT) therapy
    Other Name: Ara-C
  • Drug: Diphenhydramine
    1 mg/kg (max 50 mg) IV
    Other Name: Benadryl
  • Drug: Acetaminophen
    10 mg/kg (max 650 mg) PO x 1
    Other Name: Tylenol
  • Drug: Methylprednisolone
    1 mg/kg IV x 1
    Other Name: Solu-Medrol
Study Arms  ICMJE Experimental: Inotuzumab ozogamicin

Experimental: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

Interventions:
  • Drug: Inotuzumab ozogamicin
  • Drug: Methotrexate
  • Drug: Hydrocortisone
  • Drug: Cytarabine
  • Drug: Diphenhydramine
  • Drug: Acetaminophen
  • Drug: Methylprednisolone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 10, 2019)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2024
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Age

  • Participants must be < 22 years of age.

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% (corresponding to ECOG Score of ? 2). The Lansky performance score should be used for participants < 16 years and the Karnofsky performance score for participants ? 16 years.

Prior Therapy

  • Patients must have fully recovered from the acute toxic effects of all prior anticancer 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 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 GVHD.
  • At least 2 weeks must have elapsed since local 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 TBI was received; ? 6 weeks must have elapsed if other substantial bone marrow irradiation was given.

Organ Function Requirements

  • Adequate renal function defined as glomerular filtration rate ? 60 cc/min/1.73m2 or serum creatinine based on age as follows:

    • Age: <6 months; maximum serum creatinine (mg/dL): 0.4 (male, female); Age: 6 months to <1 year; maximum serum creatinine (mg/dL): 0.5 (male, female); Age: 1 to < 2 years; maximum serum creatinine (mg/dL): 0.6 (male, female); Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male, female); Age: 6 to <10 years; maximum serum creatinine (mg/ dL): 1 (male, female); Age: 10 to <13 years; maximum serum creatinine (mg/dL): 1.2 (male, female); Age: 13 to <16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female); Age: ? 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female)
  • Adequate hepatic function defined as:

    • Direct bilirubin ? 1.4 mg/dL (if total bilirubin > 1.4 mg/dL) and
    • AST or ALT ? 3 x ULN for age.
  • Adequate cardiac function defined as shortening fraction of ? 27% or ejection fraction ? 45%.

Exclusion Criteria:

  • History of sinusoidal obstruction 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 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 of research participant or legal guardian/representative to give written informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sima Jeha, MD866-278-5833[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03913559
Other Study ID Numbers  ICMJE INOMRD
NCI-2019-01062 ( Registry Identifier: NCI Clinical Trial Registration Program )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics ([email protected]) who will respond to the data request.
Supporting Materials:Study Protocol
Supporting Materials:Statistical Analysis Plan (SAP)
Supporting Materials:Informed Consent Form (ICF)
Time Frame:Data will be made available at the time of article publication.
Access Criteria:Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
Responsible Party St. Jude Children's Research Hospital
Study Sponsor  ICMJE St. Jude Children's Research Hospital
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Sima Jeha, MDSt. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP