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Imfinzi NSCLC
Imfinzi NSCLC

JOURNAL ONKOLOGIE – STUDIE

A Trial to Evaluate the Safety and Efficacy of oNKord® in Subjects With Acute Myeloid Leukemia

Rekrutierend

NCT-Nummer:
NCT04632316

Studienbeginn:
Dezember 2020

Letztes Update:
17.12.2020

Wirkstoff:
Cyclophosphamide-Fludarabine (Cy/Flu), oNKord®

Indikation (Clinical Trials):
Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Glycostem Therapeutics BV

Collaborator:
-

Studienleiter

Prof. Dr. Arnold Ganser, MD
Principal Investigator
Hannover Medical School (MHH), Hannover, Germany

Kontakt

Studienlocations (3 von 8)

University Medical Center Hamburg-Eppendorf
Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Hannover Medical School
Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
University Hospital Ghent
Ghent
BelgiumNoch nicht rekrutierend» Google-Maps
Institut Gustave Roussy
Villejuif
FranceNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

WiNK is a prospective 2-stage, open-label, single arm, multicentre Phase I/IIa trial to

evaluate the safety and efficacy of oNKord®, an off-the-shelf, ex vivo-cultured allogeneic NK

cell preparation, in 33 adults with acute myeloid leukemia (AML) who are in complete

morphologic remission with residual measurable disease and with no strong indication for

hematopoietic stem cell transplantation.

Following informed consent and eligibility procedures, subjects enrolled in the trial will

receive a lymphodepleting conditioning regimen consisting of cyclophosphamide and fludarabine

(Cy/Flu) followed by up to 3 oNKord® infusions 4 days apart.

Stage A of the trial (dose escalation stage) is designed to assess the safety and

tolerability of up to 3 oNKord® infusions, 4 days apart, in 3 cohorts of 3 subjects, and to

determine the oNKord® recommended Phase II dose (RP2D) to be used in Stage B.

Stage B of the trial (expansion stage) will evaluate the safety, tolerability and efficacy of

oNKord® at the RP2D in 24 subjects.

All subjects treated with oNKord® will be followed up until 12 months after the start of

treatment. Eligibility criteria for participation in the trial and follow-up duration are the

same for subjects in both Stage A and Stage B.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Male or female subjects ≥ 18 years old

2. Subjects with a diagnosis of AML and related precursor neoplasms according to the WHO

2016 classification (excluding acute promyelocytic leukemia), including secondary AML

after an antecedent hematological disease (e.g. myelodysplastic syndrome) and

therapy-related AML

3. Subjects who have achieved CMR, including CRi and complete clinical remission, with

MRD documented at screening, as assessed by centralized MFC, after one or two courses

of remission induction chemotherapy and who have completed consolidation chemotherapy

or who achieved CMR with documented MRD with hypomethylating agents or other relevant

appropriate therapies

4. Life expectancy ≥ 6 months at screening

5. Adequate renal and hepatic functions within 14 days of study screening, unless clearly

disease related, as indicated by the following laboratory values:

1. Serum creatinine ≤ 3 times the upper limit of normal (ULN) and estimated

glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2

2. Serum total bilirubin < 2.0 mg/dl, unless due to Gilbert's syndrome

3. Alanine transaminase (ALT) ≤ 2.5 x ULN

6. Karnofsky Status ≥ 50%

7. Male subjects with partners who are women of childbearing potential must use an

effective contraceptive method during the trial and for a minimum of 6 months after

trial treatment, or have undergone successful vasectomy at least 6 months prior to

entry into the trial (confirmed by semen analysis).

8. Female subjects of childbearing potential must have a negative serum pregnancy test at

screening and agree to use an effective contraceptive method during the trial and for

a minimum of 6 months after trial treatment.

9. Able to understand and willing to provide written informed consent to participate in

the trial

10. Affiliation to a national health insurance scheme (according to applicable local

requirements)

Exclusion Criteria:

1. Subjects proceeding to allogeneic HSCT, i.e. subject is a suitable candidate for

allogeneic HSCT according to the investigator's assessment and donor is expected to be

available in a timely manner

2. Subjects having received prior allogeneic HSCT

3. Subjects with acute promyelocytic leukemia

4. Diagnosis of any previous or concomitant malignancy is an exclusion criterion, except

when the subject completed treatment (chemotherapy and/or surgery and/or radiotherapy)

with curative intent for this malignancy at least 6 months prior to enrolment

5. Blast crisis of chronic myeloid leukemia

6. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes,

uncontrolled hypertension, active or uncontrolled infection) including abnormal

laboratory values, that could compromise compliance with the trial protocol or cause

unacceptable safety risks

7. Antibodies against HLA (anti-HLA) present

8. Seronegativity for Epstein-Barr Virus (EBV)

9. Known allergy to any of the components of oNKord® (e.g., dimethyl sulfoxide [DMSO]) or

to any of the drugs to be administered in the preparative regimen to oNKord® infusion

10. Contraindication to any of the drugs to be administered in the conditioning regimen or

oNKord® infusion. This includes Cy, Flu, and medications associated with prophylaxis

of AEs

11. Cardiac dysfunction as defined by:

1. Myocardial infarction within the last 3 months of trial entry, or

2. Reduced left ventricular function with an ejection fraction < 40% as measured by

multi-gated acquisition (MUGA) scan or echocardiogram (echo) within 28 days

before screening, or

3. Unstable angina, or

4. New York Heart Association (NYHA) Class IV congestive heart failure, or

5. Unstable cardiac arrhythmias

12. Pulmonary dysfunction as defined by oxygen saturation < 90% on room air. Pulmonary

function test (PFT) is required only in the case of symptomatic or prior known

impairments within 28 days before screening - with pulmonary function < 50% corrected

diffusing capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume

in 1 second (FEV1)

13. Major surgery within 4 weeks prior to screening or a major wound that has not fully

healed

14. Vaccination with live, attenuated vaccines within 4 weeks prior to screening

15. Immunosuppressive drugs for concomitant disease. Subject must be able to be off

prednisone or other immunosuppressive medications for at least 3 days prior to the

start of Cy/Flu regimen

16. History of stroke or intracranial hemorrhage within 6 months prior to screening

17. Active infections (viral, bacterial or fungal) that requires specific therapy. Acute

anti-infectious therapy must have been completed within 14 days prior to trial

treatment

18. History of human immunodeficiency virus (HIV) or active infection with hepatitis B

virus (HBV) or hepatitis C virus (HCV)

19. Current concomitant chemotherapy, radiation therapy, or immunotherapy

20. Positive pregnancy test or breastfeeding for women of childbearing potential

21. Participation in another interventional clinical trial within 4 weeks prior to trial

enrolment or participation in a concomitant interventional clinical trial

22. Any serious concomitant medical condition, medication or therapy which could, in the

opinion of the Investigator, compromise participation in the trial

23. Subjects under legal protection measure (guardianship, trusteeship or safeguard of

justice) and/or inability or unwillingness to comply with the requirements and

procedures of this trial

Studien-Rationale

Primary outcome:

1. Safety and tolerability of oNKord® using the cumulative incidence of the adverse events of special interest (AESI) (Time Frame - Up to 12 months):
AESI include: Grade 3 to 4 infusion-related toxicity of oNKord®, as rated by CTCAE v5.0; Acute GVHD grade III and IV; CRS and ICANS ≥ Grade 2, as rated by the ASTCT Consensus Grading

2. Efficacy of oNKord® using the cumulative incidence of MRD response as assessed by multiparameter flow cytometry in bone marrow (Time Frame - Up to 12 months):
Subjects with responses are defined as MRD negative subjects still in CMR at any time during the follow-up period of the trial after receiving oNKord® at RP2D

Secondary outcome:

1. Safety and tolerability of the overall trial treatment (Cy/Flu in combination with up to three oNKord® infusions) using the cumulative incidence of AESIs (Time Frame - Up to 12 months):
AESI include: Grade 3 to 4 infusion-related toxicity of oNKord® as rated by CTCAE v5.0; Acute GVHD grade III and IV; CRS and ICANS ≥ Grade 2 as rated by the ASTCT Consensus Grading; Hemorrhagic cystitis; Death related to the overall trial treatment; Incidence and severity of viral, fungal, and bacterial infections with onset during the first two months following conditioning initiation, including viral reactivations, and Infection Related Mortality defined as death due to infectious disease

2. Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on Event-free survival (EFS) (Time Frame - Up to 12 months)

3. Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on cumulative incidence of relapse (CIR) (Time Frame - Up to 12 months)

4. Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on the duration of MRD response (Time Frame - Up to 12 months)

5. Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on overall survival (OS) (Time Frame - Up to 12 months)

6. Changes in Quality of Life (EORT QLQ-C30) (Time Frame - Up to 12 months)

7. Changes in Quality of Life (SF-36) (Time Frame - Up to 12 months)

Geprüfte Regime

  • Cyclophosphamide-Fludarabine (Cy/Flu):
    Lymphodepleting conditioning regimen
  • oNKord®:
    Allogeneic ex vivo-generated Natural Killer (NK) cells from CD34+ umbilical cord blood progenitor cells

Quelle: ClinicalTrials.gov


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