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

Primary Purpose

Precursor Cell Lymphoblastic Leukemia

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Inotuzumab ozogamicin
Sponsored by
Nicola Goekbuget
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Precursor Cell Lymphoblastic Leukemia

Eligibility Criteria

56 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female patients, ≥56 years of age and contraindication for age-adapted consolidation chemotherapy due to age (≥75 years) and/or severe co-morbidities (>2 per Charlson Score).
  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 at least 20%, assessed by local/institutional flow cytometry of a bone marrow aspirate sample (assessment of CD22 via the reference lab for immunophenotyping 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 600 mg/m2) and the standard prephase treatment
  5. With or without documented CNS involvement
  6. Adequate liver function, including total serum bilirubin < 2.0 x upper limit of normal (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 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 for 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 entry on study
  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 entry on study
  16. Evidence of uncontrolled current serious active infection (including sepsis, bacteremia, fungemia or COVID-19 infection) 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 and for men at least 5 months after the last dose of investigational product

18. Participation in other studies involving investigational drug(s) (Phase I-IV) within 4 weeks before study inclusion

19. 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.

Sites / Locations

  • Klinikum AugsburgRecruiting
  • Universität BonnRecruiting
  • Klinikum Chemnitz gGmbHRecruiting
  • Uniklinik DresdenRecruiting
  • University Hospital DüsseldorfRecruiting
  • Universität ErlangenRecruiting
  • Univeristätsklinikum EssenRecruiting
  • University Hospital of FrankfurtRecruiting
  • Universitätsklinikum FreiburgRecruiting
  • Universitätsklinikum HeidelbergRecruiting
  • UniklinikumRecruiting
  • University of MuensterRecruiting
  • Klinikum Nürnberg NordRecruiting
  • Robert - Bosch - KrankenhausRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Induction Therapy with Inotuzumab Ozogamicin

Arm Description

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.

Outcomes

Primary Outcome Measures

Event free survival (EFS) at 12-months follow-up
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

Complete hematological remission
The rate of complete hematological remission after inotuzumab ozogamicin induction treatment
MRD response after induction treatment
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
Relapse free survival after two years
Molecular relapse
The proportion of patients with molecular relapse
Overall survival
Overall survival after two years
Death during induction
Death during induction
Death in complete remission
Death in complete remission

Full Information

First Posted
February 22, 2018
Last Updated
October 31, 2022
Sponsor
Nicola Goekbuget
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1. Study Identification

Unique Protocol Identification Number
NCT03460522
Brief Title
Inotuzumab Ozogamicin and Conventional Chemotherapy In Patients Aged 56 Years and Older With ALL
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 2, 2018 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nicola Goekbuget

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The trial proposed to evaluate the efficacy and safety of an inotuzumab ozogamicin followed by 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 three cycles of inotuzumab ozogamicin and intrathecal therapy only. This will be followed by a conventional maintenance therapy. All patients will be followed for cytological response, minimal residual disease and safety parameters.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Precursor Cell Lymphoblastic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Induction Therapy with Inotuzumab Ozogamicin
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Inotuzumab ozogamicin
Intervention Description
Patients will receive standard of care chemotherapy (only maintenance) after Inotuzumab Ozogamicin.
Primary Outcome Measure Information:
Title
Event free survival (EFS) at 12-months follow-up
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.
Time Frame
At 12 months
Secondary Outcome Measure Information:
Title
Complete hematological remission
Description
The rate of complete hematological remission after inotuzumab ozogamicin induction treatment
Time Frame
42 days
Title
MRD response after induction treatment
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
Time Frame
42 days
Title
Relapse free survival
Description
Relapse free survival after two years
Time Frame
two years
Title
Molecular relapse
Description
The proportion of patients with molecular relapse
Time Frame
two years
Title
Overall survival
Description
Overall survival after two years
Time Frame
two years
Title
Death during induction
Description
Death during induction
Time Frame
42 days
Title
Death in complete remission
Description
Death in complete remission
Time Frame
up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
56 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients, ≥56 years of age and contraindication for age-adapted consolidation chemotherapy due to age (≥75 years) and/or severe co-morbidities (>2 per Charlson Score). Newly diagnosed acute lymphoblastic leukemia (>25% marrow blasts, assessed by morphology; i.e. M3 marrow) Leukemic blasts must have CD22 surface expression of at least 20%, assessed by local/institutional flow cytometry of a bone marrow aspirate sample (assessment of CD22 via the reference lab for immunophenotyping 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 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 600 mg/m2) and the standard prephase treatment With or without documented CNS involvement Adequate liver function, including total serum bilirubin < 2.0 x upper limit of normal (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 Serum creatinine <1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of >40 mL/min WHO performance status ≤ 2 Signed written inform consent Inclusion in GMALL registry Exclusion Criteria: Philadelphia-chromosome or BCR-ABL positive ALL Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria Peripheral absolute lymphoblast count >10,000/μL after pre-phase treatment and before start of study medication 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) 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 for human immunodeficiency virus (HIV) Major surgery within < 4 weeks before entry on study Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function or unstable pulmonary condition) 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 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 Myocardial infarction < 6 months before entry on study 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 Uncontrolled electrolyte disorders that can confound the effects of a QTc prolonging drug (e.g., hypokalemia, hypocalcemia, hypomagnesemia) History of chronic liver disease (e.g., cirrhosis) or suspected alcohol abuse History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) Administration of live vaccine <6 weeks before entry on study Evidence of uncontrolled current serious active infection (including sepsis, bacteremia, fungemia or COVID-19 infection) or patients with a recent history (within 4 months) of deep tissue infections such as fasciitis or osteomyelitis 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 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 and for men at least 5 months after the last dose of investigational product 18. Participation in other studies involving investigational drug(s) (Phase I-IV) within 4 weeks before study inclusion 19. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Matthias Stelljes (Principal Investigator), MD
Phone
+49 (0)251 8352801
Email
stelljes@uni-muenster.de
First Name & Middle Initial & Last Name or Official Title & Degree
Julian Knaden (Study Coordinator)
Phone
+49 (0)69 6301
Ext
86369
Email
knaden@med.uni-frankfurt.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthias Stelljes, MD
Organizational Affiliation
University of Münster
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinikum Augsburg
City
Augsburg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Rank, PD Dr
Facility Name
Universität Bonn
City
Bonn
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katjana Schwab, Dr
Facility Name
Klinikum Chemnitz gGmbH
City
Chemnitz
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mathias Hänel, PD Dr
Facility Name
Uniklinik Dresden
City
Dresden
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nael Alakel, Dr.
Facility Name
University Hospital Düsseldorf
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathrin Nachtkamp, Dr
Facility Name
Universität Erlangen
City
Erlangen
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernd Spriewald, Prof
Facility Name
Univeristätsklinikum Essen
City
Essen
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maher Hanoun, PD Dr.
Facility Name
University Hospital of Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicola Gökbuget, Dr
Facility Name
Universitätsklinikum Freiburg
City
Freiburg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ralph Wäsch, Prof. Dr.
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Raffel, Dr
Facility Name
Uniklinikum
City
Jena
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sebastian Scholl, PD Dr
Facility Name
University of Muenster
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthias Stelljes, Prof Dr
Facility Name
Klinikum Nürnberg Nord
City
Nürnberg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kerstin Schäfer-Eckhardt, Dr
Facility Name
Robert - Bosch - Krankenhaus
City
Stuttgart
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sonja Martin, Dr.

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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