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

M.D. Anderson Cancer Center

Status and phase

Enrolling

Phase 2

Conditions

Follicular Lymphoma

Treatments

Drug: Diphenhydramine

Drug: Prednisone

Drug: Cyclophosphamide

Drug: Acetaminophen

Drug: Fludarabine phosphate

Drug: Axicabtagene Ciloleucel

Study type

Interventional

Funder types

Other

Identifiers

NCT06043323

2023-0087

NCI-2023-07173 (Other Identifier)

Details and patient eligibility

About

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

Full 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 or 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 complete response rate (CR) at approximately 6 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
Assess T-cell fitness from blood samples by flow cytometry and ssRNAseq prior to and after bridging RT
Perform immune profiling of blood samples for T-cell subsets prior to and after bridging RT
Assess cytokine profile after infusion

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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) on most recent biopsy, history of transformed follicular lymphoma permitted at clinician discretion)
Patients with follicular lymphoma must have disease that has relapsed or is refractory to 2 or more prior lines of systemic therapy
(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 1 measurable lesion on imaging, defined as a lesion 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.
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

History of other (non B-cell lymphoma) 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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

20 participants in 1 patient group

Axicabtagene Ciloleuce

Experimental group

Description: