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

NCT03460522 | Unknown Phase 2 DMC

• 1 other identifier: INITIAL-1
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 14

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

Conditions

Precursor Cell Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Complete hematological remission

  42 days

• MRD response after induction treatment

  42 days

• Relapse free survival

  two years

• Molecular relapse

  two years

• Overall survival

  two years

Study Arms (1)

Induction Therapy with Inotuzumab Ozogamicin

EXPERIMENTAL

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

Interventions

Inotuzumab ozogamicin DRUG

Patients will receive standard of care chemotherapy (only maintenance) after Inotuzumab Ozogamicin.

Induction Therapy with Inotuzumab Ozogamicin

Eligibility Criteria

• Age: 56 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nicola Goekbuget: lead

Study Sites (14)

Klinikum Augsburg

Augsburg, Germany

RECRUITING

Universität Bonn

Bonn, Germany

RECRUITING

Klinikum Chemnitz gGmbH

Chemnitz, Germany

RECRUITING

Uniklinik Dresden

Dresden, Germany

RECRUITING

University Hospital Düsseldorf

Düsseldorf, 40225, Germany

RECRUITING

Universität Erlangen

Erlangen, Germany

RECRUITING

Univeristätsklinikum Essen

Essen, Germany

RECRUITING

University Hospital of Frankfurt

Frankfurt, 60590, Germany

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Uniklinikum

Jena, Germany

RECRUITING

University of Muenster

Münster, 48149, Germany

RECRUITING

Klinikum Nürnberg Nord

Nuremberg, Germany

RECRUITING

Robert - Bosch - Krankenhaus

Stuttgart, Germany

RECRUITING

Related Publications (1)

• Stelljes M, Raffel S, Alakel N, Wasch R, Kondakci M, Scholl S, Rank A, Hanel M, Spriewald B, Hanoun M, Martin S, Schwab K, Serve H, Reiser L, Knaden J, Pfeifer H, Marx J, Sauer T, Berdel WE, Lenz G, Bruggemann M, Gokbuget N, Wethmar K. Inotuzumab Ozogamicin as Induction Therapy for Patients Older Than 55 Years With Philadelphia Chromosome-Negative B-Precursor ALL. J Clin Oncol. 2024 Jan 20;42(3):273-282. doi: 10.1200/JCO.23.00546. Epub 2023 Oct 26.

  PMID: 37883727 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Matthias Stelljes, MD

  Universität Münster

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthias Stelljes (Principal Investigator), MD

CONTACT

+49 (0)251 8352801; stelljes@uni-muenster.de

Julian Knaden (Study Coordinator)

CONTACT

+49 (0)69 6301; knaden@med.uni-frankfurt.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of GMALL

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: March 9, 2018
• Study Start: May 2, 2018
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 2, 2022

Record last verified: 2022-10

Locations

DE (14)