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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06043323

Collaborator

(none)

Enrollment

Arm

53.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma	Drug: Axicabtagene Ciloleucel Drug: Cyclophosphamide Drug: Fludarabine phosphate Drug: Prednisone Drug: Diphenhydramine Drug: Acetaminophen	Phase 2

Detailed 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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 31, 2024

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Sep 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Axicabtagene Ciloleuce Participants will first have a procedure to collect your white blood cells that will be used to make axicabtagene ciloleucel. Then participatns will receive radiation therapy, followed by conditioning chemotherapy and 1 infusion of axicabtagene ciloleucel.	Drug: Axicabtagene Ciloleucel Given by IV (vein) Drug: Cyclophosphamide Given by IV (vein) Other Names: Cytoxan® Neosar® Drug: Fludarabine phosphate Given by IV (vein) Drug: Prednisone Given by IV (vein) Drug: Diphenhydramine Given by IV (vein) Other Names: Benadryl® Drug: Acetaminophen Given by IV (vein) Other Names: Tylenol® Dorcol® Feverall Panadol APAP N-Acetyl-P-Aminophenol Paracetamo Ofirmev™

Arm

Intervention/Treatment

Experimental: Axicabtagene Ciloleuce

Participants will first have a procedure to collect your white blood cells that will be used to make axicabtagene ciloleucel. Then participatns will receive radiation therapy, followed by conditioning chemotherapy and 1 infusion of axicabtagene ciloleucel.

Drug: Axicabtagene Ciloleucel

Given by IV (vein)

Drug: Cyclophosphamide

Given by IV (vein)

Other Names:

Cytoxan®

Neosar®

Drug: Fludarabine phosphate

Given by IV (vein)

Drug: Prednisone

Given by IV (vein)

Drug: Diphenhydramine

Given by IV (vein)

Other Names:

Benadryl®

Drug: Acetaminophen

Given by IV (vein)

Other Names:

Tylenol®

Dorcol®

Feverall

Panadol

APAP

N-Acetyl-P-Aminophenol

Paracetamo

Ofirmev™

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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)
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.