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

• Status: Recruiting
• Trial end date: 2022-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cellex Patient Treatment GmbH
• Collaborator: PHARMALOG Institut für klinische Forschung GmbH
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

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