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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Precursor Cell Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Inotuzumab ozogamicin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 65
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Matthias Stelljes (Principal Investigator), MD; Phone Number: +49 (0)251 8352801; Email: stelljes@uni-muenster.de
• Study Contact Backup: Name: Julian Knaden (Study Coordinator); Phone Number: 86369 +49 (0)69 6301; Email: knaden@med.uni-frankfurt.de

Study Locations

• Germany
  • Augsburg, Germany
    • Recruiting
    • Klinikum Augsburg
    • Contact: Andreas Rank, PD Dr
  • Bonn, Germany
    • Recruiting
    • Universitat Bonn
    • Contact: Katjana Schwab, Dr
  • Chemnitz, Germany
    • Recruiting
    • Klinikum Chemnitz gGmbH
    • Contact: Mathias Hänel, PD Dr
  • Dresden, Germany
    • Recruiting
    • Uniklinik Dresden
  • Düsseldorf, Germany, 40225
    • Recruiting
    • University Hospital Düsseldorf
    • Contact: Kathrin Nachtkamp, Dr
  • Erlangen, Germany
    • Recruiting
    • Universität Erlangen
    • Contact: Bernd Spriewald, Prof
  • Essen, Germany
    • Recruiting
    • Univeristätsklinikum Essen
    • Contact: Maher Hanoun, PD Dr.
  • Frankfurt, Germany, 60590
    • Recruiting
    • University Hospital of Frankfurt
    • Contact: Nicola Gökbuget, Dr
  • Freiburg, Germany
    • Recruiting
    • Universitätsklinikum Freiburg
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitätsklinikum Heidelberg
    • Contact: Simon Raffel, Dr
  • Jena, Germany
    • Recruiting
    • Uniklinikum
    • Contact: Sebastian Scholl, PD Dr
  • Münster, Germany, 48149
    • Recruiting
    • University of Muenster
    • Contact: Matthias Stelljes, Prof Dr
  • Nürnberg, Germany
    • Recruiting
    • Klinikum Nürnberg Nord
    • Contact: Kerstin Schäfer-Eckhardt, Dr
  • Stuttgart, Germany
    • Recruiting
    • Robert - Bosch - Krankenhaus
    • Contact: Sonja Martin, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Inotuzumab ozogamicin; Patients will receive standard of care chemotherapy (only maintenance) after Inotuzumab Ozogamicin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Nicola Goekbuget
• Investigators: Principal Investigator: Matthias Stelljes, MD, University of Munster

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2018
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: February 22, 2018
• First Submitted That Met QC Criteria: March 2, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Inotuzumab Ozogamicin
• Other Study ID Numbers: INITIAL-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No