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Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT03104491
Recruitment Status : Recruiting
First Posted : April 7, 2017
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
Leland Metheny, Case Comprehensive Cancer Center

Brief Summary:

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects.

The Phase II portion of this study is to see what side effects are seen with medication after transplant.

Inotuzumab ozogamicin is a combination of an antibody and chemotherapy. This means that it targets the acute lymphocytic leukemia (ALL) cell and can deliver the chemotherapy to the ALL cell. Research shows that in some patients, it has caused their disease to go back into remission.

Inotuzumab ozogamicin is considered experimental in this study.


Condition or disease Intervention/treatment Phase
Cluster of Differentiation Antigen (CD22)-Positive Acute Lymphoblastic Leukemia Drug: Inotuzumab Ozogamicin Phase 1 Phase 2

Detailed Description:

Primary Objective Phase I: To define a post hematopoietic stem cell transplantation maximum tolerated dose of inotuzumab Ozogamicin Phase II: To define the safety profile of inotuzumab Ozogamicin therapy after allogeneic transplant.

Phase II: To determine the rate of veno-occlusive disease / sinusoidal obstruction syndrome (VOD/SOS).

Secondary Objective(s)

  1. To evaluate non-relapse mortality (NRM), relapse, relapse-related mortality and overall survival (OS) at 1 year.
  2. To determine the incidence of myeloid toxicity and secondary graft failure.
  3. To determine if inotuzumab at these doses are effective at eradicating minimal residual disease (MRD) in this cohort of patients.

Study Design This is a Phase I/II study of inotuzumab ozogamicin for the treatment of patients who underwent allogeneic transplantation for ALL and have a high risk of relapse. The Phase I portion of this study will be a 3/3 dose escalation trial with cohort expansion at the maximum tolerated dose (MTD). Subjects will receive study treatment until relapse of disease, unacceptable toxicity, 30 days after cycle 4, or death, whichever occurs first.

Phase I: Inotuzumab Ozogamicin Dosing Escalation Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach.

Phase II: Inotuzumab Ozogamicin Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach. In order to be included in the safety profile endpoint review, subjects must have received at least of 1 cycle of treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Inotuzumab Ozogamicin Post-Transplant for Acute Lymphocytic Leukemia
Actual Study Start Date : March 21, 2017
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: Inotuzumab Ozogamicin
Subjects will be assessed for safety and tolerability (including adverse events, serious adverse events, and clinical/laboratory assessments) using a continuous monitoring approach.
Drug: Inotuzumab Ozogamicin
Participants will begin at 0.6mg/m2 and will be adjusted in 0.1mg/m2 increments using a dose escalation scale depending on tolerability. Total range of dose levels is 0.1-0.6mg/m2




Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: Up to 112 days (16 weeks) ]
    Phase I Primary Outcome

  2. Post transplant relapse rate [ Time Frame: Up to 1 year after initial treatment ]
    Phase II Primary Outcome: number of patients with relapse after stem cell transplant


Secondary Outcome Measures :
  1. Response Rate [ Time Frame: Up to 1 year after initial treatment ]
    defined as the proportion of patients with a best overall response of eradicating MRD in this cohort of patients at the time each patient discontinues treatment with Inotuzumab Ozogamicin

  2. Recurrence-free survival [ Time Frame: Up to 1 year after initial treatment ]
    Time from initial treatment to progression, death, or one year, whichever comes first

  3. Overall Survival [ Time Frame: Up to 1 year after initial treatment ]
    Time from initial treatment to death or one year, whichever comes first

  4. Incidence of myeloid toxicity [ Time Frame: Up to 1 year after initial treatment ]
    Number of patients who develop myeloid toxicity while on study

  5. Incidence of secondary graft failure [ Time Frame: Up to 1 year after initial treatment ]
    Number of patients who develop secondary graft failure while on study



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Phase I

Inclusion Criteria:

  • Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
  • Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • Patients who are between T+40 and T+100 after allogeneic transplantation. Patients must receive their first dose of inotuzumab at or before T+100.
  • Patients who have/are either:

    • Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation

      • Pre- or Post-Transplant Minimal Residual Disease defined by:

        • Any detectable ALL (by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) techniques) as per clinical indication.
    • In second or third complete remission at the time of allogeneic transplantation
    • Treated with reduced intensity regimens
    • Lymphoid blast crisis of CML
    • Are relapsed or refractory to at least 1 line of chemotherapy
    • Philadelphia-like ALL
  • Patients who have evidence of donor chimerism after allogeneic transplantation.
  • Philadelphia chromosome positive ALL must have failed at least 1 Tyrosine kinase inhibitors (TKI)
  • Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document.
  • Subjects must have ANC > 1,000 for 3 days and platelet transfusion independence as defined as a platelet count > 50,000 for 7 days.

Phase II

Inclusion Criteria:

  • Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
  • Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
  • Patients who are between T+40 and T+100 after allogeneic transplantation
  • Patients who have/are either:

    • Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation

      • Post-Transplant Minimal Residual Disease defined by:

        • Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication.
    • In second or third complete remission at the time of allogeneic transplantation
    • Treated with reduced intensity regimens
    • Lymphoid blast crisis of CML
    • Are relapsed or refractory to at least 1 line of chemotherapy
    • Philadelphia-like ALL
  • Patients who have ≥80% donor chimerism after allogeneic transplantation.
  • Philadelphia chromosome positive ALL must have failed at least 1 TKI
  • ECOG Performance status ≤ 2
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document.
  • Subjects must have ANC > 1,000 for 3 days and platelet transfusion independence as defined as a platelet count > 20,000 for 7 days

Phase I/II

Exclusion Criteria:

  • Patients with inadequate Organ Function as defined by:

    • Creatinine clearance < 30ml/min
    • Bilirubin ≥ 2 times institutional upper limit of normal
    • Aspartate aminotransferase (AST SGOT) ≥ 2 times institutional upper limit of normal
    • Alanine aminotransferase (ALT SGPT) ≥ 2 times institutional upper limit of normal
  • GVHD grade III or IV.
  • Active acute or chronic graft-versus-host disease (GVHD) of the liver
  • History of VOD
  • Active malignancy
  • Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or breastfeeding women are excluded from this study
  • Participation in any other investigational drug study or had exposure to any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
  • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
  • Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds

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): NCT03104491


Contacts
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Contact: Leland Metheny, MD 216-844-0139 leland.metheny@uhhospitals.org
Contact: Ron Sobecks, MD 216-444-6833 sobeckr@ccf.org

Locations
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United States, Ohio
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Leland Metheny, MD    216-983-4946    Leland.Metheny@uhhospitals.org   
Principal Investigator: Leland Metheny         
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Suspended
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Leland Metheny
Investigators
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Principal Investigator: Leland Metheny, MD University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

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Responsible Party: Leland Metheny, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03104491     History of Changes
Other Study ID Numbers: CASE1916
First Posted: April 7, 2017    Key Record Dates
Last Update Posted: June 26, 2019
Last Verified: June 2019

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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 Leland Metheny, Case Comprehensive Cancer Center:
allogeneic hematopoietic stem cell transplantation
donor chimerism
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Inotuzumab Ozogamicin
Antineoplastic Agents