NCT06002659

CAR20(NAP)-T Therapy for B Cell Lymphoma (CARMA-01 Study)

A Phase I/IIa Multicenter Study Evaluating the Safety and Efficacy of CAR20(NAP)-T in Patients With Relapsed/Refractory B Cell Lymphoma (CARMA-01 Study)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Uppsala University · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

The purpose is to study the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CAR20(NAP)-T for patients with B-cell malignancies.

Detailed description

A cancer patient's T cells can be isolated and engineered to express a chimeric antigen receptor (CAR), which re-directs the T cells to recognize and kill tumor cells expressing that particular antigen. CD19-targeted CAR-T cell therapy has shown good effects for B cell malignancies, even cure, in otherwise therapy refractory patients. Antigen escape, i.e., the downregulation of the antigen targeted by the CAR due to the selective pressure caused by the CAR-T cell therapy is a challenge. For patients treated with CD19 CAR-T cell therapy, about 30% of the patients are resistant to treatment and about 20% of patients relapse after an initial response. CAR20(NAP)-T cells target CD20 and upon target recognition secrete a bacterial-derived pluripotent immune-stimulating factor named NAP (Helicobacter pylori Neutrophil-activating protein). Secretion of NAP in the tumor microenvironment can induce an endogenous bystander immune response, that counteracts antigen escape and thereby improves the therapeutic outcome. CAR20(NAP)-T is an investigational agent not yet approved by authorities. Design: The study is designed as 3+3 dose escalation phase I, and a dose expansion Phase IIa. The safety, tolerability, PK/PD, and efficacy will be evaluated.Dose escalation is to be based on the incidence of dose-limiting toxicity (DLTs). The investigator or sub-investigator will decide if the AE is related to IMP-treatment on a case-by-case basis depending on the character of the DLT symptoms. Investigator or sub-investigator has a possibility to classify various toxicity observed in patient as DLT.The Recommended phase II dose (RP2D) is decided based on safety, PK/PD data as well as preliminary clinical activity data from the Phase I dose escalation. After setting the RP2D, additional patients will be treated at RP2D to make sure at least 6 patients will be treated at RP2D dose level already at the phase I part. Protocol treatment: The enrolled patient will undergo a leukapheresis procedure to harvest enough T cells for IMP production. During CAR20(NAP)-T manufacturing, the patient may receive bridging therapy to control tumor burden. All patients will receive pre-conditioning chemotherapy (cyclophosphamide and fludarabine) followed by one dose of CAR20(NAP)-T cell infusion intravenously. The patient will then be followed by doctor/study nurse for evaluation of the health status and side effects. At follow-up visits, blood samples will be obtained and CT imaging will be performed. Patient will actively participate in the study for about 24 months when the final follow-up visit will be scheduled.

Conditions

• B-cell Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	CAR20(NAP)-T	Autologous CAR-T cells targeting CD20 and upon target recognition express and secrete NAP
DRUG	Cyclophosphamide	pre-conditioning chemotherapy
DRUG	Fludarabine	pre-conditioning chemotherapy

Timeline

• Start date: 2024-05-01
• Primary completion: 2027-12-30
• Completion: 2027-12-30
• First posted: 2023-08-21
• Last updated: 2024-05-09

Locations

2 sites across 1 country: Sweden