A study evaluating the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Subjects with High-Risk Large B-Cell Lymphoma

Phase 1

• Conditions: Adult subjects with high-risk large B-cell lymphoma, including either high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 translocations (double-hit or triple-hit lymphomas) or International Prognostic Index (IPI) score =3.; MedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002291-13-FR
• Lead Sponsor: Kite Pharma, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-10
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

101. Histologically confirmed large B-cell lymphoma, including the following types defined by WHO 2016 (Swerdlow et al, 2016):
? - Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including Germinal center B-cell (GCB) type and activated B-cell (ABC) type; Intravascular large B-cell lymphoma; T-cell/histiocyte-rich large B-cell lymphoma; DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV + DLBCL, NOS;
? - High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit)
? - High-grade B-cell lymphoma, NOS

102. High risk large B-cell lymphoma, defined as one or more of the following:
? High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations (double-hit or triple-hit) as determined by investigator by fluorescent in situ hybridization (FISH)
OR
? International Prognostic Index (IPI) score of =3 at initial diagnosis or anytime between initial diagnosis and enrolment

103. Subjects must have a positive interim PET per Cheson, 2014 (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy as follows:
? 2 cycles of a dose intense anti-CD20 monoclonal antibody and anthracycline containing regimen (e.g. DA-EPOCH-R) x 2 cycles with or without intrathecal chemotherapy at the discretion of the investigator per standard of care for double-hit or triple-hit lymphoma
OR
? 2 cycles of a standard anti-CD20 monoclonal antibody and anthracycline containing regimen (e.g. R-CHOP) for large B-cell lymphoma with IPI score of =3

104. At least 2 weeks must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis

105. No evidence, suspicion and/or history of CNS involvement of lymphoma

106. Toxicities due to prior therapy must be stable and recovered to = Grade 1 (except for clinically non-significant toxicities such as alopecia)

107. Age 18 or older

108. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

109. ANC = 1000/µL

110. Platelet count = 75,000/µL

111. Absolute lymphocyte count = 100/µL

112. Adequate renal, hepatic, pulmonary, and cardiac function defined as:
a. Creatinine clearance (as estimated by Cockcroft Gault) = 60 mL/min
b. Serum ALT/AST =2.5 ULN
c. Total bilirubin =1.5 mg/dL, except in subjects with Gilbert’s syndrome

113. Cardiac ejection fraction = 50% , no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings

114. No clinically significant pleural effusion

115. Baseline oxygen saturation > 92% on room air

116. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

201. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years

202. History of Richter’s transformation of CLL or PMBCL

203. History of autologous or allogeneic stem cell transplant

204. Prior CD19-targeted therapy

205. Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy

206. History of severe, immediate hypersensitivity reaction attributed to aminoglycosides

207. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management; simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the sponsor’s medical monitor

208. History of HIV infection or acute or chronic active hepatitis B or C infection; subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines or applicable country guidelines

209. Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter); dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted

210. Subjects with detectable cerebrospinal fluid malignant cells, brain metastases, or active CNS lymphoma

211. History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

212. Subjects with cardiac atrial or cardiac ventricular lymphoma involvement

213. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment

214. Requirement for urgent therapy due to tumor mass effects (eg, blood vessel compression, bowel obstruction, or transmural gastric involvement)

215. Primary immunodeficiency

216. History of autoimmune disease (eg, Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years

217. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment

218. Any medical condition likely to interfere with assessment of safety or efficacy of study treatment

219. History of severe immediate hypersensitivity reaction to any of the agents used in this study

220. Live vaccine = 6 weeks prior to planned start of conditioning regimen

221. Women of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for
at least 2 years are not considered to be of childbearing potential

222. Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy

223. In the investigator’s judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified