Clinical Trials /

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

NCT03460522

Description:

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

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

    <li>Brief Title: Inotuzumab Ozogamicin and Conventional Chemotherapy In Patients Aged 56 Years and Older With ALLli><li>Official Title: 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)li>

Clinical Trial IDs

    <li>ORG STUDY ID: INITIAL-1li><li>NCT ID: NCT03460522li>

Conditions

    <li>Precursor Cell Lymphoblastic Leukemiali>

Interventions

DrugSynonymsArms
Inotuzumab ozogamicinInduction Therapy with Inotuzumab Ozogamicin

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Induction Therapy with Inotuzumab OzogamicinExperimentalPatients 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.
    <li>Inotuzumab ozogamicinli>

Eligibility Criteria

        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/&#956;L 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.
      
Maximum Eligible Age:74 Years
Minimum Eligible Age:56 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event free survival (EFS) at 12-months follow-up
Time Frame:At 12 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Complete hematological remission
Time Frame:42 days
Safety Issue:
Description:The rate of complete hematological remission after inotuzumab ozogamicin induction treatment
Measure:MRD response after induction treatment
Time Frame:42 days
Safety Issue:
Description: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
Measure:Relapse free survival
Time Frame:two years
Safety Issue:
Description:Relapse free survival after two years
Measure:Molecular relapse
Time Frame:two years
Safety Issue:
Description:The proportion of patients with molecular relapse
Measure:Overall survival
Time Frame:two years
Safety Issue:
Description:Overall survival after two years
Measure:Death during induction
Time Frame:42 days
Safety Issue:
Description:Death during induction
Measure:Death in complete remission
Time Frame:up to 2 years
Safety Issue:
Description:Death in complete remission

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Nicola Goekbuget

Last Updated

<p/>