A Phase II Study of Axicabtagene Ciloleucel, an Anti-CD19 Chimeric Antigen Receptor (CAR) Tcell Therapy, in Combination With Radiotherapy (RT) in Relapsed/Refractory Follicular Lymphoma

Follicular Lymphoma Clinical Trial

Official title:

A Phase II Study of Axicabtagene Ciloleucel, an Anti-CD19 Chimeric Antigen Receptor (CAR) Tcell Therapy, in Combination With Radiotherapy (RT) in Relapsed/Refractory Follicular Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06043323
• Other study ID #: 2023-0087
• Status: Recruiting
• Phase: Phase 2
• Start date: January 8, 2024
• Est. completion date: September 1, 2028

Study information

• Verified date: June 2024
• Source: M.D. Anderson Cancer Center
• Contact: Susan Wu, MD
• Phone: (281) 630-7607
• Email: sywu1[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To learn about the safety of a drug called axicabtagene ciloleucel given in combination with radiation therapy to patients with relapsed/refractory FL.

Description:

Primary Objectives:

-The primary objective of this study is to determine the safety of standard of care axicabtagene ciloleucel with bridging radiotherapy (RT) in patients with relapsed/refractory follicular lymphoma, as assessed by the incidence of grade 3 or higher cytokine release syndrome (CRS) within 30 days after chimeric antigen receptor (CAR) T-cell infusion.

Secondary Objectives:

• Establish the rates of CRS and ICANS in patients treated with CAR T-cell therapy and radiation

• Determine complete response rate (CR) at approximately 1 month post CAR T-cell ---therapy

• Determine the overall response rate (ORR)

• Determine the duration of response (DOR)

• Determine progression free survival (PFS)

• Determine overall survival (OS)

Exploratory Objectives:

-Assess the impact of tumor burden as measured by metabolic tumor volume and total lesion glycolysis on PET/CT on response following CAR T-cell infusion

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 1, 2028
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Eligible subjects will be considered for inclusion if they meet all of the following criteria:

• Men and women 18 years of age or older

• Histologically proven FL (Grade 1-3A)

• Relapsed or refractory following 2 or more prior lines of systemic therapy

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Medically appropriate for CAR-T cell therapy: adequate organ function CrCL >/= 45 mL/min/m2, hemoglobin level = 8 g/dl, serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels = 2.5 × upper limit of normal (ULN) or = 5 x ULN if documented liver involvement, baseline oxygen saturation levels (SpO2) =92% on room air

• Have at least 2 measurable lesions on imaging, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) and =1 cm on CT, MRI, or clinical exam. At least one lesion will be omitted from the radiation treatment field.

• Prior radiation therapy is permitted provided normal tissue tolerance is not exceeded

• Female of child-bearing potential (FOCBP, defined below) must have a negative pregnancy test within 1 week of simulation for RT

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Histologic evidence of transformed follicular lymphoma, or follicular lymphoma grade 3B

• History of invasive malignancy requiring active therapy (systemic therapy, radiation, or surgery) within the past 3 years, excluding non-melanomatous skin cancer

• Women of childbearing potential who are pregnant

• Women who are breastfeeding and unwilling to discontinue prior to lymphodepleting chemotherapy and for 12 months following lymphodepleting chemotherapy and CAR-T cell infusion

• Urgent need for bridging chemotherapy or rituximab between apheresis and CAR T cell product infusion (steroids permitted)

• Additional RT would exceed standard organ at risk constraints

• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides

• Uncontrolled fungal, bacterial, or viral infection requiring intravenous antimicrobials for management. Urinary tract infection and uncomplicated bacterial pharyngitis is permitted if responding to active treatment. Recent COVID19 infection is permitted if patient is deemed medically stable for CAR-T cell therapy.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Axicabtagene Ciloleucel
Given by IV (vein)
• Cyclophosphamide
Given by IV (vein)
• Fludarabine phosphate
Given by IV (vein)
• Prednisone
Given by IV (vein)
• Diphenhydramine
Given by IV (vein)
• Acetaminophen
Given by IV (vein)

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0		through study completion; an average of 1 year

External Links

•   M D Anderson Cancer Center