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Inotuzumab Ozogamicin and Conventional Chemotherapy In Patients Aged 56 Years and Older With ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03460522
Recruitment Status : Active, not recruiting
First Posted : March 9, 2018
Last Update Posted : May 4, 2021
Information provided by (Responsible Party):
Nicola Goekbuget, Goethe University

Tracking Information
First Submitted Date  ICMJE February 22, 2018
First Posted Date  ICMJE March 9, 2018
Last Update Posted Date May 4, 2021
Actual Study Start Date  ICMJE May 2, 2018
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2018)
Event free survival (EFS) at 12-months follow-up [ Time Frame: At 12 months ]
An event is any of the following: persisting bone marrow blasts (more than 5% leukemic blasts) after two cycles of inotuzumab ozogamicin, relapse or death.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2018)
  • Complete hematological remission [ Time Frame: 42 days ]
    The rate of complete hematological remission after inotuzumab ozogamicin induction treatment
  • MRD response after induction treatment [ Time Frame: 42 days ]
    The rate of patients being negative for minimal residual disease (defined by RQ-PCR for at least one leukemia-specific IG/TR gene rearrangement or leukemia specific genetic aberration with a sensitivity of at least 10-4) after induction treatment
  • Relapse free survival [ Time Frame: two years ]
    Relapse free survival after two years
  • Molecular relapse [ Time Frame: two years ]
    The proportion of patients with molecular relapse
  • Overall survival [ Time Frame: two years ]
    Overall survival after two years
  • Death during induction [ Time Frame: 42 days ]
    Death during induction
  • Death in complete remission [ Time Frame: up to 2 years ]
    Death in complete remission
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Inotuzumab Ozogamicin and Conventional Chemotherapy In Patients Aged 56 Years and Older With ALL
Official Title  ICMJE Open Label Phase II Study to Evaluate the Efficacy and Safety of Inotuzumab Ozogamicin for Induction Followed by Chemotherapy Consolidation and Maintenance Therapy In Patients Aged 56 Years and Older With Acute Lymphoblastic Leukemia (ALL)
Brief Summary The trial proposed to evaluate the efficacy and safety of an inotuzumab ozogamicin followed by an age-adapted intermediate intensive consolidation therapy and maintenance treatment in patients with acute lymphoblastic leukemia older than 56 years
Detailed Description

Despite recent advances especially in younger patients, the prognosis of elderly patients with ALL remains dismal with a 5-year survival rate of around 20%, even after intensive chemotherapy.

Inotuzumab ozogamicin (PF-05208773; CMC-544) is an antibody-targeted intravenous (IV) chemotherapy agent composed of an anti-CD22 antibody linked to calicheamicin, a potent cytotoxic antitumor antibiotic.

After a prephase treatment, induction therapy will be based on inotuzumab ozogamicin and intrathecal therapy only. After a maximum of three cycles, patients will receive an age adapted intermediate dose consolidation chemotherapy based on the backbone of the German Multicenter Study Group for adult ALL (GMALL). This will be followed by a conventional maintenance therapy. All patients will be followed for cytological response, minimal residual disease and safety parameters.

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 Precursor Cell Lymphoblastic Leukemia
Intervention  ICMJE Drug: Inotuzumab ozogamicin
Patients will receive standard of care chemotherapy (consolidation and maintenance) after Inotuzumab Ozogamicin.
Study Arms  ICMJE Experimental: Induction Therapy with Inotuzumab Ozogamicin
Patients will receive up to 3 cycles Inotuzumab with applications on day 1, 8 and 15 in each cycle. First dose will be 0.8 mg/m² on Day 1. All subsequent doses will be 0,5 mg/m².
Intervention: Drug: Inotuzumab ozogamicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 2, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female patients, ≥56 years of age and fit for therapy
  2. Newly diagnosed acute lymphoblastic leukemia (>25% marrow blasts, assessed by morphology; i.e. M3 marrow)
  3. Leukemic blasts must have CD22 surface expression of a least 20%, assessed by local/institutional flow cytometry of a bone marrow aspirate sample (assessment of CD22 via the reference lab for immungenetics is strongly recommended). In the case of an inadequate aspirate sample (dry tap), flow cytometry of peripheral blood specimen may be substituted if the patient has circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
  4. No previous ALL-specific treatment with the exception of corticosteroids and/or single dose vincristine and/or a maximum of three doses of cyclophosphamide (cumulative dose of 600mg/m2) and the standard prephase treatment
  5. With or without documented CNS involvement
  6. Adequate liver function, including total serum bilirubin <2.0 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) <2.5 x ULN If organ function abnormalities are considered due to leukemic infiltration of the liver, total serum bilirubin must be < 2.5 x ULN and AST/ALT <5 x ULN
  7. Serum creatinine <1.5 x upper limit of normal (ULN) or any serum creatinine level associated with a measured or calculated creatinine clearance of >40 mL/min
  8. WHO performance status ≤ 2
  9. Signed written inform consent
  10. Inclusion in GMALL registry

Exclusion Criteria:

  1. Philadelphia-chromosome or BCR-ABL positive ALL
  2. Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria
  3. Peripheral absolute lymphoblast count >10,000/μL after pre-phase treatment and before start of study medication
  4. Known systemic vasculitis (e.g. , Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIV infection or severe inflammatory disease)
  5. Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity or human immunodeficiency virus (HIV)
  6. Major surgery within <4 weeks before entry on study
  7. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function or unstable pulmonary condition)
  8. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery; patients with previous malignancies are eligible provided that they have been disease free for >2 years
  9. Cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than 45%, or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure
  10. Myocardial infarction <6 months before randomization
  11. History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block or higher degrees of AV block unless a permanent pacemaker has been implanted
  12. Uncontrolled electrolyte disorders that can confound the effects of a QTc prolonging drug (e.g., hypokalemia, hypocalcemia, hypomagnesemia)
  13. History of chronic liver disease (e.g., cirrhosis) or suspected alcohol abuse
  14. History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)
  15. Administration of live vaccine <6 weeks before randomization
  16. Evidence of uncontrolled current serious active infection (including sepsis, bacteremia, fungemia) or patients with a recent history (within 4 months) of deep tissue infections such as fasciitis or osteomyelitis
  17. Patients who have had a severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibodies or any known hypersensitivity to the active substance or any of its excipients
  18. Pregnant females; breastfeeding females; males and females of childbearing potential (a woman is considered of childbearing potential (WOCBP) i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile e.g. after hysterectomy or bilateral ovariectomy. Please refer to chapter 12.4 Contraceptive Requirements.) not using highly effective contraception or not agreeing to continue highly effective contraception for women at least 8 months an for men at least 5 months after the last dose of investigational product
  19. Participation in other studies involving investigational drug(s) (Phase I-IV) within 4 weeks before study inclusion
  20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 56 Years to 74 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03460522
Other Study ID Numbers  ICMJE INITIAL-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Nicola Goekbuget, Goethe University
Study Sponsor  ICMJE Nicola Goekbuget
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Matthias Stelljes, MD University of Münster
PRS Account Goethe University
Verification Date May 2021

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