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

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

NCT ID: NCT06002659

Condition: B-cell Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Cyclophosphamide
Fludarabine

Conditions: Keywords:
CAR T cell
B cell lymphoma
CD20
HP-NAP

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: CAR20(NAP)-T
Description: Autologous CAR-T cells targeting CD20 and upon target recognition express and secrete NAP
Arm group label: Treatment

Other name: ELC-301

Intervention type: Drug
Intervention name: Cyclophosphamide
Description: pre-conditioning chemotherapy
Arm group label: Treatment

Intervention type: Drug
Intervention name: Fludarabine
Description: pre-conditioning chemotherapy
Arm group label: Treatment

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.

Criteria for eligibility:
Criteria:
Key Inclusion Criteria: - Signed informed consent. - Relapsed or refractory CD20+ diffuse large B-cell lymphoma, mantle cell lymphoma or indolent lymphoma. - The patient should have been treated with at least two lines of therapy and have no curative treatment option, specifically - Relapsed or refractory CD20+ B-cell lymphoma that are not eligible to receive clinically approved CD19-directed CAR T cell treatment. - Relapsed or refractory CD20+ B-cell lymphoma who are CD19 negative. - Relapsed or refractory B-cell lymphoma who relapse after CD19 CAR T cell treatment. - In phase I age >18 years, in phase II all ages - Measurable disease per Lugano classification. - Performance status ECOG 0-2. - Adequate bone marrow function as evidenced by: - Absolute neutrophil count (ANC) ≥ 1x10^9/l/L - Platelet ≥ 50x 10^9/l - Absolute lymphocyte count ≥ 0,1x10^9/L - Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by: - Creatinine clearance (Cockcroft Gault) ≥ 30 mL/min - Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN) and S-Bilirubin <1.5x UNL - Cardiac ejection fraction ≥ 40% - Functional venous for administration of IMP. - Fertile individuals must consent to use contraceptives during participation in the trial. Exclusion Criteria: - Other CD20-positive lymphomas i.e Burkitt lymphoma, primary CNS lymphoma, plasmablastic lymphoma or CLL transformed to DLBCL/HGBL (Richter transformation) - Any significant medical or psychiatric illness that would prevent the subject from giving informed consent or from following the study procedures. - Known human immunodeficiency virus (HIV) infection. - Impending organ-compromising disease. - Rapidly progressing disease - Active and/or severe infection (e.g., tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. - Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the subject to perform the treatment. - Treatment with an investigational product within 30 days prior to enrolment - Potential sign of hypersensitivity reaction to tocilizumab or any of the agents used in this study - Systemic corticosteroid treatment (>10mg/day) <5 days prior to IMP treatment or <7 days prior leukapheresis. - Pregnancy

Gender: All

Minimum age: N/A

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Karolinska University Hospital

Address:
City: Stockholm
Country: Sweden

Status: Active, not recruiting

Facility:
Name: Uppsala University Hospital

Address:
City: Uppsala
Country: Sweden

Status: Recruiting

Contact:
Last name: Gunilla Enblad

Investigator:
Last name: Gunilla Enblad, MD/PhD
Email: Principal Investigator

Start date: May 1, 2024

Completion date: December 30, 2027

Lead sponsor:
Agency: Uppsala University
Agency class: Other

Collaborator:
Agency: Elicera Therapeutics
Agency class: Other

Collaborator:
Agency: Uppsala University Hospital
Agency class: Other

Collaborator:
Agency: Karolinska University Hospital
Agency class: Other

Source: Uppsala University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06002659