臨床研究等提出・公開システム

A Phase 2 Multicenter, Open-label, Single-arm Study of KTE-C19 in Japanese Patients with Refractory or Relapsed Large B Cell Lymphoma

A Phase 2 Multicenter, Open-label, Single-arm Study of KTE-C19 in Japanese Patients with Refractory or Relapsed Large B Cell Lymphoma

17

The median age was 57.0 years (range: 44 to 70 years). Most of the participants were male, < 65 years old, and diagnosed with DLBCL.

Of the 17 enrolled patients, 16 patients were received study treatment and 1 patient was not received study treatment due to disease progression. Reason for ending study for participants treated with axicabtagene ciloleucel were as follows: Death (9 patients), Rollover to KT-US-982-5968 LTFU study (5 patients) , Full consent withdrawal (2 patients) .

Adverse events were reported for all 100% patients (16 of 16 patients) treated with Axi-cel. Same percentage of patients experienced Grade 3 or higher AEs. Any CRS were reported for 81% patients (13 of 16 patients) treated with Axi-cel and 6% patients (1 of 16 patients) experienced Grade 3 or higher CRS. No neurologic event was reported. Any infection AE were reported for 75% patients (12 of 16 patients) treated with Axi-cel and 13% patients (2 of 16 patients) experienced Grade 3 or higher infection AE. Any cytopenia were reported for 94% patients (16 of 16 patients) treated with Axi-cel and same percentage of patients experienced Grade 3 or higher cytopenia. No fatal AEs were reported. The most common AEs were pyrexia(88%) and platelet count decreased(50%)

ORR was 86.7%; 13 of 15 patients

Complete Response Rate was 53.5%; 8 of 15 patients, Partial Response Rate was 33.3%; 5 of 15 patients, Stable disease rate was 6.7%; 1 of 15 patients, Progressive disease rate was 6.7%; 1 of 15 patients. the median time to response (TTR) was 0.953 months. The median OS time was 54.2 months at the end of the study.

Efficacy and safety were evaluated when Axi-cel was administered in patients with refractory or relapsed large B-cell lymphoma. ORR (primary efficacy endpoint) was 86.7% thus, the efficacy of Axi-cel was demonstrated. Reported AEs were generally reversible and manageable. No significant additional safety concerns of Axi-cel were raised.

Jan. 31, 2025

No

Aso Hiroya

Gilead Sciences, K.K.

1-9-2, Marunouchi, Chiyoda-ku, Tokyo, 100-6616, Japan

ClinicalTrialGSJ@gilead.com

Clinical Operations

Gilead Sciences, K.K.

1-9-2, Marunouchi, Chiyoda-ku, Tokyo, 100-6616, Japan

+81-3-6837-0710

JPClinicalOperations@gilead.com

completed

Oct. 29, 2018

Interventional

- Non-randomized - Open-label - Single-arm - No control group

treatment purpose

2

A subject who satisfies all the criteria below will be enrolled in the study.
1) Histologically confirmed aggressive B-cell NHL (including the following types defined by the WHO 2016)
i) DLBCL
a) DLBCL, NOS
- Germinal center B-cell lymphoma
- Activated B-cell lymphoma
b) Intravascular large B-cell lymphoma
c) T-cell/histiocyte-rich large B-cell lymphoma
d) DLBCL associated with chronic inflammation
e) Epstein-Barr virus (EBV)positive diffuse large B-cell lymphoma, NOS
ii) PMBCL
iii) TFL
iv) High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement
v) High-grade B-cell lymphoma, NOS
2) Chemotherapy-refractory disease, defined as one or more of the following:
i) No response to first-line therapy (primary refractory disease); subjects who are intolerant to first-line therapy chemotherapy are excluded
a) Progressive Disease (PD) as best response to first-line therapy
b) Stable Disease (SD) as best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP) with SD duration no longer than 6 months from last dose of therapy
ii) No response to second or greater lines of therapy
a) PD as best response to most recent therapy regimen
b) SD as best response after at least 2 cycles of last line of therapy with SD duration no longer than 6 months from last dose of therapy
iii) Relapsed post-ASCT
a) Disease progression or relapsed =< 12 months of ASCT (must have biopsy proven relapse in relapsed subjects)
b) if salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy (must have biopsy proven recurrence in relapsed subjects)
3) Subjects must have received at least the following therapy:
i) Anti-CD20 monoclonal antibody (unless the investigator or subinvestigator determines that tumor is CD20 negative)
ii) An anthracycline containing chemotherapy regimen;
iii) Prior chemotherapy for follicular lymphoma for subjects with transformed TFL (subsequently have a chemorefractory disease after transformation to DLBCL)
4) At least 1 measurable lesion according to the revised IWG Response Criteria for Malignant Lymphoma (Cheson 2007). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy

A patient who meets any of the following criteria is not eligible.
1) History of malignancy within the past 3 years (patients with skin cancer [except for melanoma] or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma are eligible even with a history within 3 years)
2) History of Richter's transformation of CLL
3) Autologous stem cell transplant within 6 weeks of planned KTE-C19 infusion
4) History of allogeneic stem cell transplant
5) Prior CD19 targeted therapy (except for subjects who are eligible for re-treatment of KTE-C19 in this study)
6) Prior CAR T cell therapy or other genetically modified T cell therapy (except for subjects who are eligible for re-treatment of KTE-C19 in this study)

Both

Refractory or relapsed (relapse after transplant or relapse after medication in patients ineligible for transplant) diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL), transformed follicular lymphoma (TFL) or High-grade B cell lymphoma

investigational material(s)
Generic name etc : Anti-CD19 CAR T cells
INN of investigational material : axicabtagene ciloleucel
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : KTE-C19 will be administered to achieve target dose of anti-CD19 CAR T cells 2.0 X 10^6 cells/kg. For a subject weighing > 100 kg, KTE-C19 will be administered to achieve the maximum fixed dose of 2.0 X 10^8 cells.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
- ORR (percentage of patients judged CR or PR) assessed by the investigator or subinvestigator based on the criteria of the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma (Cheson 2007)

safety
efficacy
exploratory
pharmacokinetics
other
- ORR assessed by the central image evaluation organization
- DOR
- PFS
- OS

May. 10, 2018