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JOURNAL ONKOLOGIE – STUDIE

Dose-escalating Trial With UniCAR02-T Cells and CD123 Target Module (TM123) in Patients With Hematologic and Lymphatic Malignancies

Rekrutierend

NCT-Nummer:
NCT04230265

Studienbeginn:
Januar 2020

Letztes Update:
13.11.2020

Wirkstoff:
Cyclophosphamide (Non-IMP), Fludarabine (Non-IMP), TM123 (IMP), UniCAR02-T (IMP)

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Cellex Patient Treatment GmbH

Collaborator:
PHARMALOG Institut für klinische Forschung GmbH

Studienleiter

Martin Wermke, MD
Principal Investigator
Universitätsklinikum Carl Gustav Carus Dresden

Kontakt

Studienlocations (3 von 5)

Onkologisches Zentrum Universitätsklinikum Würzburg
Josef-Schneider-Straße 6
97080 Würzburg
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Sabrina Kraus, MD
E-Mail: kraus_s3@ukw.de
» Ansprechpartner anzeigen
Gynäkologisches Tumorzentrum am Universitätsklinikum Leipzig
4103 Leipzig
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Vladan Vucinic, MD
E-Mail: vladan.vucinic@medizin.uni-leipzig.de
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

This dose-escalating phase I trial assesses for the first time the safety, the side effects

and the harmlessness, as well as the therapeutical benefit of the new study drug

UniCAR02-T-CD123 in patients with hematologic and lymphatic malignancies positive for CD123

marker. The UniCAR02-T-CD123 drug is a combination of a cellular component (UniCAR02-T) with

a recombinant antibody derivative (TM123) which together forms the active drug.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Male or female patients, age ≥ 18 years

2. Documented definitive diagnosis at screening of AML, B-ALL or BPDCN (according to

standard of care testing) and CD123 positivity of more than 20 % of blasts.

- Relapsed or refractory AML,

- Relapsed or refractory B-ALL (in patients aged over 25 years or over 18 years

without access to an approved chimeric antigen receptor (CAR)-T cell product at

time point of potential inclusion into this study),

- Patients with histological and/or cytological evidence of BPDCN in the peripheral

blood, bone marrow (BM), spleen, lymph nodes, skin, and/or other sites that is

persistent/recurrent following prior standard of care treatment for BPDCN

3. Eastern Cooperative Oncology Group (ECOG) of 0 to 1

4. Life expectancy of at least 2 months

5. Adequate renal and hepatic laboratory assessments:

6. Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF) of ≥ 45 % as

assessed by transthoracic two-dimensional echocardiography

7. Permanent venous access existing (e.g. port-system) resp. acceptance of implantation

of a device

8. Able to give written informed consent

9. Weight ≥ 45 kg

10. Negative pregnancy; routinely using a highly effective method of birth control

Exclusion Criteria:

1. Acute promyelocytic leukemia (t15;17) and T-ALL

2. Manifestation of AML, ALL or BPDCN in central nervous system

3. Bone marrow failure syndromes

4. Cardiac disease: i.e. heart failure (NYHA III or IV); unstable coronary artery

disease, myocardial infarction or serious cardiac ventricular arrhythmias requiring

anti-arrhythmic therapy within the last 6 months prior to study entry

5. Patients undergoing renal dialysis

6. Pulmonary disease with clinical relevant hypoxia

7. Parkinson, epilepsy and, stroke or presence or history of seizures, paresis, aphasia

or intracranial hemorrhage

8. History or presence of disseminated intravascular coagulation (DIC) or thromboembolism

9. Hemolytic anemia

10. Multiple sclerosis

11. Active infectious disease considered by investigator to be incompatible with protocol

or being contraindications for lymphodepletion therapy

12. Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow

obstruction

13. Allogeneic stem cell transplantation within last two months or Graft versus host

disease (GvHD) requiring immunosuppressive therapy

14. Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy

15. Major surgery within 28 days

16. Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed

17. Treatment with any investigational drug substance or experimental therapy within 4

weeks or 5 half-lives (whatever is shorter) of the substance prior to the day of

apheresis

18. Prior treatment with gene therapy products

19. Use of checkpoint inhibitors within 5 half-lives of the respective substance

20. Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants

21. Pregnant or breastfeeding women

22. Psychologic disorders, drug and/or significant active alcohol abuse

23. Known history of human immunodeficiency virus (HIV) or active/chronic infection with

hepatitis C virus (HCV) or hepatitis B virus (HBV)

24. Presence of autoantibodies against La/Sjögren syndrome (SS)-B or presence or history

of autoimmune diseases

25. Known hypersensitivity to cellular component (UniCAR02-T) and/or targeting module

(TM123) excipients or to compounds of the lymphodepletion therapy or tocilizumab or

corticosteroids

26. Evidence suggesting that the patient is not likely to follow the study protocol

27. Incapability of understanding purpose and possible consequences of the trial

28. Patients who should not be included according to the opinion of the investigator

Studien-Rationale

Primary outcome:

1. Safety and tolerability (Time Frame - DLT period (infusion period of TM123 + 7 days or + 28 days in patients with complete blast clearance) until Safety Follow-up 1 (infusion period of TM123 + 28 days + 3 months)):
Incidence and intensity of adverse events graded according to CTCAE V5.0

2. Incidence of dose limiting toxicity (DLT) (Time Frame - DLT period (infusion period of TM123 + 7 days or + 28 days in patients with complete blast clearance)):
DLT is defined as any adverse Event at least possible related to TM123 and/or UniCAR02-T

3. Maximum tolerated dose (MTD) (Time Frame - DLT period (infusion period of TM123 + 7 days or + 28 days in patients with complete blast clearance)):
The dose for which the isotonic estimate of the DLT probability is closest to the target DLT probability of 0.2.

Secondary outcome:

1. Recommended phase 2 dose (RP2D) (Time Frame - DLT period (infusion period of TM123 + 7 days or + 28 days in patients with complete blast clearance)):
The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.

2. Complete remission (CR), incomplete remission (CRi) and partial remission (PR) (Time Frame - until fifteen years after last UniCAR02-T administration):
CR: Bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 Gpt/L and platelet count > 100 Gpt/L. Level of MRD should be measured in patients achieving CR in case as suitable marker exists. CRi: All criteria for CR except residual thrombocytopenia (platelets < 100 Gpt/L) and/or neutropenia (absolute neutrophil count < 1 Gpt/L). PR: All hematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50 %.

3. Disease stabilization (DS) (Time Frame - until fifteen years after last UniCAR02-T administration):
Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR.

4. Best response rate (Time Frame - until fifteen years after last UniCAR02-T administration):
The best observed response during observational period. Response states are ordered descending as follows: CR > CRi > PR > DS > refractory disease.

5. Progression free survival (PFS) (Time Frame - until fifteen years after last UniCAR02-T administration):
The time from first treatment with TM123 and UniCAR02-T until disease progression or death. If no progress of death was observed during the observational period, the patient's progression free survival time will be censored on the date the patient was last seen progression-free and alive.

6. Overall survival (OS) (Time Frame - until fifteen years after last UniCAR02-T administration):
The number of days between the first study drug administration and death from any cause. If death was not observed during the observational period, the patient's overall survival time will be censored on the date the patient was last seen alive.

Geprüfte Regime

  • Cyclophosphamide (Non-IMP):
    Intravenous infusion for 3 days
  • Fludarabine (Non-IMP):
    Intravenous infusion for 3 days
  • TM123 (IMP):
    Intravenous Infusion for 25 days
  • UniCAR02-T (IMP):
    Intravenous infusion of single dose

Quelle: ClinicalTrials.gov


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