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Trial record 69 of 115 for:    cancer | butyrate

Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT03913559
Recruitment Status : Recruiting
First Posted : April 12, 2019
Last Update Posted : October 16, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

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).

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Drug: Inotuzumab ozogamicin Drug: Methotrexate Drug: Hydrocortisone Drug: Cytarabine Drug: Diphenhydramine Drug: Acetaminophen Drug: Methylprednisolone Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia
Actual Study Start Date : May 14, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : January 2024


Arm Intervention/treatment
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

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




Primary Outcome Measures :
  1. Treatment response Cycle1 - count [ Time Frame: At the end of cycle 1 (each cycle is 28 days) ]
    Number of patients that reach MRD negative at the end of cycle 1

  2. Treatment Response Cycle 1 - percentage [ Time Frame: At the end of cycle 1 (each cycle is 28 days) ]
    Percentage of patients that reach MRD negative at the end of cycle 1

  3. Treatment Response Cycle 2 - count [ Time Frame: At the end of cycle 2 (each cycle is 28 days) ]
    Number of patients that reach MRD negative at the end of cycle 2

  4. Treatment Response Cycle 2 - percentage [ Time Frame: At the end of cycle 2 (each cycle is 28 days) ]
    Percentage of patients that reach MRD negative at the end of cycle 2


Secondary Outcome Measures :
  1. 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 ]
    Number of patient deaths that occur at any time during observation on study

  2. 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 ]
    Percentage of patient deaths that occur at any time during observation on study

  3. 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 ]
    Number of patients that develop VOD at any time during observation on study

  4. 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 ]
    Percentage of patients that develop VOD at any time during observation on study



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 or research participant or legal guardian/representative to give written informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03913559


Contacts
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Contact: Sima Jeha, MD 866-278-5833 referralinfo@stjude.org

Locations
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United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Sima Jeha, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Sima Jeha, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Pfizer
Investigators
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Principal Investigator: Sima Jeha, MD St. Jude Children's Research Hospital

Additional Information:
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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT03913559     History of Changes
Other Study ID Numbers: INOMRD
NCI-2019-01062 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: April 12, 2019    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
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 (ClinTrialDataRequest@stjude.org) who will respond to the data request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Jude Children's Research Hospital:
B-cell Acute Lymphoblastic Leukemia
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Neoplasms
Hydrocortisone 17-butyrate 21-propionate
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Acetaminophen
Diphenhydramine
Promethazine
Cytarabine
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Hydrocortisone
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Methotrexate
Inotuzumab Ozogamicin
Prednisolone hemisuccinate
Prednisolone phosphate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs