CAR T cell treatment in Elderly Patients with First-Relapsed or Primary Refractory B-cell Non-Hodgkin Lymphoma
- Conditions
- malignant disease of lymphnodes especially refractory and non-responding aggressive non Hodgkin lymphomaDiffuse large B cell lymphoma (DLBCL)MedDRA version: 23.0Level: PTClassification code 10029601Term: Non-Hodgkin's lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002930-35-DE
- Lead Sponsor
- niveristy of Cologne
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 28
1. Written, signed and dated informed consent
2. Patients with first relapse of aggressive B-cell Non-Hodgkin’s Lymphoma (aNHL) within 365 days after rituximab- and anthracycline-containing first-line immunochemotherapy or aNHL refractory to respective 1st-line therapy (no achievement of a CR or PR) who are ineligible for either autologous or allogeneic stem cell transplantation, defined as age > 65 years, or > 60 years old with HCT-CI score >2 and not older than 80 years
3. Histologically confirmed aNHL as defined by a list of subtypes
4. Measurable disease:
Nodal lesions >15 mm in the long axis, regardless of the length of the short axis,
and/or
Extranodal lesions (outside lymph node or nodal mass, but including liver and spleen) >10 mm in long AND short axis
5. ECOG performance status 0-2
6. Adequate organ function:
o Serum creatinine of =1.5 x ULN, or estimated glomerular filtration rate (GFR) = 30mL/min/1.73m2
o Hepatic function defined as:
? ALT and AST = 5 × ULN, except for aNHL-related functional impairment.
? Bilirubin = 2.0 mg/dL except for patients with Gilbert syndrome who may be included if their total bilirubin is = 3.0 × ULN and direct bilirubin = 1.5 × ULN OR for aNHL-related functional impairment
o Adequate bone marrow function
o Minimum level of pulmonary function
7. Life expectancy of more than six months
8. Women have to be in menopausal or post-menopausal status or confirmed as not having potential on childbearing. Male participants with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18
1. Patients with Richter’s transformation, Burkitt lymphoma, and PCNSL
2. Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene therapy product
3. Treatment with any lymphoma-directed second line anticancer therapy prior to enrollment with the exception of intermittent steroid therapy. After enrollment, bridging therapy is permitted for disease control
4. Patients with active CNS involvement
5. Prior autologous or allogeneic stem cell transplantation (HSCT)
6. Active hepatitis B, hepatitis C, or hepatitis E infection
7. HIV-positive patients
8. Uncontrolled acute life-threatening bacterial, viral or fungal infection (e.g. blood culture positive = 72 hours prior to infusion)
9. Cardiac dysfunction
10. Previous or concurrent malignancy with the exceptions
11. Women of childbearing potential (WOCBP), pregnant or lactating women
12. Intolerance to the excipients of the tisagenlecleucel cell product
13. Active or history of inflammatory disorders or autoimmune disease that required systemic steroids or immunosuppressive medications, with exception of vitiligo or resolved childhood asthma
14. Active tuberculosis
15. Exposure to any investigational agent(s) within 4 weeks prior to study entry
16. Chemotherapy less than 2 weeks before leukapheresis
17. Simultaneous radiotherapy to tisagenlecleucel infusion (radiotherapy between leukapheresis and day -6 before tisagenlecleucel infusion is permitted)
18. Ongoing necessity for systemic corticosteroids >10mg daily prednisone equivalent. Inhaled or topical steroids and adrenal replacement steroid doses > 10mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
19. History of active primary immunodeficiency
20. Major surgery (defined as opening at least one body cavity) within 4 weeks prior to study entry
21. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening CT scan
22. Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibodies, other immune checkpoint inhibitors
23. Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
24. Current treatment within another therapeutic clinical trial with experimental and not approved drugs and treatment combinations
25. Patient’s lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly
26. Non-compliance
27. Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator
28. Committal to an institution on judicial or official order
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method