Treatment for relapsed or refractory B-cell lymphoma using CAR T-cell therapy

Multicentre Phase I/IIa Study of Infusion of Autologous Peripheral Blood T Lymphocytes Expanded and Genetically Modified Using Sleeping Beauty Family Transposons to Express a Chimeric Antigenic Receptor With Anti-CD19 Specificity Conjugated to the 4-1BB Co-stimulatory Region and CD3z and huEGFRt Signal Transmission (TranspoCART19) in Patients With Relapsed or Refractory B-cell Lymphoma

This study is testing a new CAR T-cell therapy called TranspoCART19 to see if it can help people with relapsed or refractory B-cell lymphoma feel better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Instituto de Investigación Biomédica de Salamanca (Academic / other)
• Drugs / interventions: CAR-T, prednisone
• Locations: 8 sites (Barcelona, Barcelona and 7 other locations)
• Trial ID: NCT06378190 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a new CAR T-cell therapy called TranspoCART19 in patients with relapsed or refractory B-cell lymphoma. It consists of two phases: Phase I focuses on determining the maximum tolerated dose (MTD) using a dose escalation design, while Phase II involves an expansion cohort using the MTD established in Phase I. Participants will be monitored for a total of 36 months to assess response rates and safety outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with relapsed or refractory B-cell lymphoma and a life expectancy of at least 2 months.

Not a fit: Patients who may benefit from other approved curative therapies or those with contraindications for lymphapheresis may not receive benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with limited prognosis due to relapsed or refractory B-cell lymphoma.

How similar studies have performed: Other studies using CAR T-cell therapy have shown promising results in treating similar conditions, indicating a potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Patients diagnosed with relapsed or refractory B-cell lymphoma (Diffuse large B-cell lymphoma, Primary diffuse large B-cell lymphoma of the Central Nervous System (CNS), Mantle cell lymphoma, Follicular lymphoma grades 1, 2 or 3a or Marginal lymphoma, including splenic, nodal and MALT).
2. Age over 18 years and under 80 years.
3. Functional status Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. Patients with ECOG 2 may be included if motivated by haematological disease (Annex 3).
4. Adequate bone marrow haematopoietic reserve.
5. Life expectancy of at least 2 months.
6. Adequate venous access for lymphapheresis. Absence of contraindications for lymphapheresis.
7. Signed informed consent (patient or legal guardian).

Exclusion Criteria:

1. Patients who, in the opinion of a physician, may benefit from other approved potentially curative therapeutic options, including commercial CAR-Ts.
2. Treatment with any experimental or non-commercialised substance in the four weeks prior to recruitment, or who are actively participating in another therapeutic clinical trial.
3. Diagnosis of another neoplasm, past or present. Patients who have been in complete remission for more than 3 years, or with a history of non-melanoma skin cancer or completely resected carcinoma in situ may be included. A current or previous history of clonal T-lymphocytes is also an exclusion criterion.
4. Early relapse after allogeneic haematopoietic stem cell transplantation (less than 3 months for lymphapheresis, less than 6 months for TranspoCART19 infusion) or patients on active immunosuppressive treatment for graft-versus-recipient disease (corticosteroids or other systemic immunosuppressants).
5. Active infection requiring systemic medical treatment.
6. HIV infection.
7. Concurrent and uncontrolled medical illnesses including cardiac, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological or psychiatric illnesses that in the opinion of the investigator pose a risk to the patient.
8. Positive serology for hepatitis B, defined as a positive test for HBsAg. In addition, if the patient is HBsAg negative but has anti-HBcore antibodies, a hepatitis B virus DNA test will be required, and if the result is positive the patient will be excluded.
9. Positive serology for hepatitis C virus (HCV), defined as a positive test for anti-HCV antibodies that is confirmed by Recombinant immunoblot assay (RIBA).
10. Severe organ involvement, defined as cardiac ejection fraction \<40%; diffusing capacity of the lungs for carbon monoxide (DLCO) \<40%; calculated glomerular filtration rate \<30 ml/min; baseline O2 saturation \<92%; bilirubin \> 2 times upper limit of normal (unless due to Gilbert's syndrome) or transaminases \> 2.5 upper limit of normal.
11. Pregnant or lactating women. Women of childbearing age should have a negative pregnancy test at screening.
12. Women of childbearing age, including those whose last menstrual cycle was in the year prior to screening, who are unable or unwilling to use highly effective methods of contraception\* from the start of the study until the end of the study.
13. Men who are unable or unwilling to use highly effective methods of contraception\* from the start of the study until the end of the study.
14. Need to take glucocorticoids chronically in doses greater than 10 mg/day of prednisone (or equivalent) or other chronic immunosuppressants.
15. Previous anti-CD19 CAR-T therapy. Previous treatment with other anti-CD19 strategies is permitted, provided that CD19 expression has been confirmed in the tumour biopsy.
16. Hypersensitivity to the active substance or to any of the excipients.

Where this trial is running

Barcelona, Barcelona and 7 other locations

• Hospital Clínic — Barcelona, Barcelona, Spain (Not_yet_recruiting)
• Institut Català d'Oncologia Hospital — L'Hospitalet de Llobregat, Barcelona, Spain (Recruiting)
• Fundación Jiménez Díaz Hospital — Madrid, Madrid, Spain (Recruiting)
• Virgen de la Arrixaca University Hospital — El Palmar, Mur, Spain (Recruiting)
• Clínica Universidad de Navarra — Pamplona, Navarre, Spain (Recruiting)
• University Hospital of Navarra — Pamplona, Navarre, Spain (Recruiting)
• Salamanca University Health Care Complex — Salamanca, Salamanca, Spain (Recruiting)
• Virgen del Rocio Hospital — Seville, Sevilla, Spain (Recruiting)

Study contacts

• Study coordinator: Esperanza López_Franco, PhD

Conditions Refractory B-Cell Lymphoma; B-cell Lymphoma Recurrent