Axi-cel in CNS Lymphoma

NCT04608487 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-274
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This research is being done to test the safety and effectiveness of axicabtagene ciloleucel (axi-cel), an anti-CD19 directed chimeric antigen receptor (CAR) T-cell therapy in treating relapsed/refractory central nervous system (CNS) lymphoma, systemic lymphoma with concurrent CNS lymphoma, or systemic lymphoma with a history of treated CNS lymphoma, and to better understand what causes neurological toxicity following treatment with axi-cel. The names of the study drug(s) involved in this study are:

• axicabtagene ciloleucel (axi-cel)
• ludarabine will be given with axicel to help axicel work more effectively
• cyclophosphamide will be given with axicel to help axicel work more effectively

Conditions

Lymphoma; Lymphoma Cns

Keywords

relapsed/refractory central nervous system (CNS) lymphoma; systemic lymphoma with concurrent CNS lymphoma; systemic lymphoma with a history of treated CNS lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

  Measured by the rate of TLTs and the rate of grade 3+ adverse events (AEs) regardless of attribution

  Enrollment until 30 days after last dose of study treatment up to 24 Months

Secondary Outcomes (5)

• Objective response rate (ORR)

  2 years

• Complete response (CR) rate

  2 years

• Duration of response (DOR)

  2 years

• Progression-free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

Study Arms (1)

Fludarabine + Cyclophosphamide + Axicabtagene Ciloleucel

EXPERIMENTAL

Prior to receiving axi-cel, participants will undergo leukapheresis and the need for a Ommaya reservoir placement will be assessed and administered. Day -5 to Day -3 of 28 day study cycle Fludarabine and cyclophosphamide; Day -1 admitted to hospital, receive axi-cel on day 0; Till at least cycle day 7 hospital monitoring; post treatment follow up will occur on day 14 and day 28 of cycle 1, monthly in cycles 2, 3, 6, 9,12,15,18,21,24, then yearly after cycle 24.

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Axicabtagene Ciloleucel

Interventions

Fludarabine DRUG

Intravenous infusion

Also known as: Fludara

Fludarabine + Cyclophosphamide + Axicabtagene Ciloleucel

Cyclophosphamide DRUG

Intravenous infusion

Also known as: Cytoxan, Neosar

Fludarabine + Cyclophosphamide + Axicabtagene Ciloleucel

Axicabtagene Ciloleucel BIOLOGICAL

Intravenous infusion

Also known as: Yescarta

Fludarabine + Cyclophosphamide + Axicabtagene Ciloleucel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with relapsed/refractory active primary or secondary CNS lymphoma, histologically proven aggressive B cell lymphoma, including DLBCL, HGBL, PMBL, or tFL, and defined by the following categories:
• Primary CNS lymphoma, relapsed or refractory following at least one line of CNS-directed therapy. There is no restriction on the number of recurrences.
• Secondary CNS lymphoma, relapsed or refractory following at least one line of CNS-directed therapy for prophylaxis or treatment of CNS lymphoma.
• Radiographically event CNS disease by MRI of the brain (ie enhancing lesion on gadolinium enhanced MRI)
• For patients with secondary CNSL with concurrent systemic lymphoma, the concurrent systemic lymphoma must be either DLBCL, PMBL, high grade B cell lymphoma, or transformed lymphoma and must have relapsed following at least 1 prior lines of therapy (which must have included an anti-CD20 monoclonal antibody (unless the tumor is CD20 negative) and an anthracycline
• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic cancer therapy at the time the subject provides consent
• Age 18 years or older at the time of informed consent
• ECOG performance status of 0 or 1
• Adequate bone marrow, renal, hepatic, pulmonary and cardiac function defined as:
• Absolute neutrophil count (ANC) ≥1000/μL
• Platelet count ≥ 75,000/μL
• Absolute lymphocyte count ≥ 100/μL
• Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
• Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome

You may not qualify if:

• Primary vitreoretinal lymphoma and intraocular PCNSL without evidence of brain disease. Patients with prior history of intraocular involvement treated only with intraocular methotrexate and no prior systemic therapy are excluded
• PCNSL patients who cannot undergo magnetic resonance imaging assessments
• Patients with brain stem lesions
• Patients with leptomeningeal disease only without brain parenchymal involvement
• Bulky leptomeningeal disease and or CSF protein ≥100 mg/dL
• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
• History of Richter's transformation of CLL
• History of allogeneic stem cell transplant
• Prior CD19 targeted therapy
• Treatment with systemic immunostimulatory agents (including but not limited to interferon and IL-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of axicabtagene ciloleucel or SOC
• Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
• Active tuberculosis

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Kite, A Gilead Company: collaborator

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma; Recurrence

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; axicabtagene ciloleucel

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Caron Jacobson, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: October 29, 2020
• Study Start: December 4, 2020
• Primary Completion: June 14, 2025
• Study Completion (Estimated): June 14, 2038
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)