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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03460522

Studienbeginn:
Mai 2018

Letztes Update:
02.11.2022

Wirkstoff:
Inotuzumab ozogamicin

Indikation (Clinical Trials):
Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoid

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Nicola Goekbuget

Collaborator:
-

Studienleiter

Matthias Stelljes, MD
Principal Investigator
University of Münster

Kontakt

Matthias Stelljes (Principal Investigator), MD
Kontakt:
Phone: +49 (0)251 8352801
E-Mail: stelljes@uni-muenster.de» Kontaktdaten anzeigen
Julian Knaden (Study Coordinator)
Kontakt:
Phone: +49 (0)69 6301
Phone (ext.): 86369
E-Mail: knaden@med.uni-frankfurt.de» Kontaktdaten anzeigen

Studienlocations
(3 von 14)

Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. 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.



Secondary outcome:

1. Complete hematological remission (Time Frame - 42 days):
The rate of complete hematological remission after inotuzumab ozogamicin induction treatment

2. 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

3. Relapse free survival (Time Frame - two years):
Relapse free survival after two years

4. Molecular relapse (Time Frame - two years):
The proportion of patients with molecular relapse

5. Overall survival (Time Frame - two years):
Overall survival after two years

6. Death during induction (Time Frame - 42 days):
Death during induction

7. Death in complete remission (Time Frame - up to 2 years):
Death in complete remission

Geprüfte Regime

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

Quelle: ClinicalTrials.gov


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