Main info

Identificatie:

HOVON 161 CART / NHL

Sponsor:

UMCG

Working group party:

Lymphoma

Age:

>= 18

Stadium:

3de lijn

Echelon:

Level A

Included patients:

113

(of 300)

Active sites:

7

(of 7)

Title:

A phase II non-inferiority study comparing point-of-care produced CAR T-cell to commercial CAR T-cells in patients with relapsed/refractory Non-Hodgkin Lymphoma

Timeline

News

Details

Phase:

Prospective randomized Phase II study

Monitoring Type:

Study Specific

Objectives:

Primary study objective

• To compare progression free survival (PFS) of patients randomized to investigational point-of-care (PoC) ARI-0001 CAR T-cells versus PFS of patients randomized to commercial standard-of-care (SoC) (axicabtagene ciloleucel (Axi-cel, Yescarta)) CAR T-cells in patients with R/R DLBCL.

Secondary study objectives

• To evaluate response rates (ORR and CR).
• To evaluate safety and toxicity of ARI-0001 and Axi-cel.
• To assess overall survival (OS).
• To evaluate quality of life (QoL).
• To assess costs associated with both treatment regimens (ARI-0001 vs Axi-cel).
• To evaluate CAR T-cell expansion, persistence, and T-cell characteristics in both treatment arms (ARI-0001 vs Axi-cel).
• To evaluate PoC CAR T-cell production characteristics (e.g. number of viable T-cells, transduction efficiency, T-cell subsets (activated T-cells, memory T-cells)), including the functional characteristics (e.g. potency tests) between the different production sites.
• To evaluate the association of the functional characteristics (e.g. potency tests) of the CAR T-cell products (ARI-0001 CAR T-cells) with CAR T-cell expansion, persistence, adverse events, response rates and progression free survival.
• To assess the proportion of successful batches between the different production sites.
• To evaluate the number of days between leukapheresis and infusion of CAR T-cells (vein-to-vein time).

Eligibility

Inclusion Criteria:

• Histologically confirmed DLBCL and associated subtypes, defined by WHO 2016 classification: DLBCL not otherwise specified (NOS), High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B, T-cell/histocyte rich B-cell lymphoma, Primary mediastinal B-cell lymphoma, transformed lymphoma (transformed follicular) and R/R after at least 2 lines of systemic therapy
• Age ≥ 18
• Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0-2 (appendix D)
• If the patient has a history of central nervous system (CNS) involvement, then he/she must have
  • No signs or symptoms of CNS involvement
  • No active disease on magnetic resonance imaging (MRI)
  • Absence of large cell lymphoma in cerebral spinal fluid (CSF) on cytospin preparation or flow cytometry, regardless of the number of white blood cells
• Estimated life expectancy of >3 months other than primary disease
• Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen
• Signed and dated informed consent before conduct of any trial-specific procedure
• Patient is capable of giving informed consent

Exclusion Criteria:

• Absolute neutrophil count (ANC) <1.0x109/L
• Platelet count <50x109/L
• Absolute lymphocyte count <0.1x109/L
• Primary CNS lymphoma
• Known history of infection with hepatitis C or B virus unless treated and confirmed to be polymerase chain reaction (PCR) negative
• Active HIV infection with detectable viral load or CD4 T-cell count below 0.20x10^9/L
• Known history or presence of seizure activities or on active anti- seizure medications within the previous 12 months
• Known history of CVA within prior 12 months
• Unstable neurological deficits
• Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease
• Active systemic autoimmune disease for which immunnosupressive therapy is required
• Presence of CNS disease that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity, baseline dementia that would interfere with therapy or monitoring, determined using mini-mental status exam at baseline
• Active systemic fungal, viral or bacterial infection
• Clinical heart failure with New York Heart Association class ≥2 (appendix F) or Left Ventricular Ejection Fraction (LVEF) <40%
• Resting oxygen saturation <92% on room air
• Liver dysfunction as indicated by total bilirubin, AST and/or ALT >5 x institutional ULN, unless directly attributable to the lymphoma or Gilbert disease
• GFR <40 mL/min calculated according to the modified formula of Cockcroft and Gault or by direct urine collection
• Pregnant or breast-feeding woman
• Active other malignancy requiring treatment
• Medical condition requiring prolonged use of systemic immunosuppressives with exception of prednisolone <10 mg/day
• History of severe immediate hypersensitivity reaction against any drug or its Ingredients/ impurities that is scheduled to be given during trial participation e.g. as part of the mandatory lymphodepletion protocol, premedication for infusion, or rescue medication/salvage therapies for treatment related toxicities
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals