Clinical Trials List
Protocol NumberCCTL019E2202
NCT Number(ClinicalTrials.gov Identfier)NCT03568461
Completed
2019-12-01 - 2020-05-12
Phase II
Terminated1
ICD-10C82.00
Follicular lymphoma grade I, unspecified site
ICD-10C82.09
Follicular lymphoma grade I, extranodal and solid organ sites
ICD-10C82.10
Follicular lymphoma grade II, unspecified site
ICD-10C82.19
Follicular lymphoma grade II, extranodal and solid organ sites
ICD-10C82.20
Follicular lymphoma grade III, unspecified, unspecified site
ICD-10C82.29
Follicular lymphoma grade III, unspecified, extranodal and solid organ sites
ICD-10C82.30
Follicular lymphoma grade IIIa, unspecified site
ICD-10C82.39
Follicular lymphoma grade IIIa, extranodal and solid organ sites
ICD-10C82.40
Follicular lymphoma grade IIIb, unspecified site
ICD-10C82.49
Follicular lymphoma grade IIIb, extranodal and solid organ sites
ICD-10C82.50
Diffuse follicle center lymphoma, unspecified site
ICD-10C82.59
Diffuse follicle center lymphoma, extranodal and solid organ sites
ICD-10C82.60
Cutaneous follicle center lymphoma, unspecified site
ICD-10C82.69
Cutaneous follicle center lymphoma, extranodal and solid organ sites
ICD-10C82.80
Other types of follicular lymphoma, unspecified site
ICD-10C82.89
Other types of follicular lymphoma, extranodal and solid organ sites
ICD-10C82.90
Follicular lymphoma, unspecified, unspecified site
ICD-10C82.99
Follicular lymphoma, unspecified, extranodal and solid organ sites
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9202.00
Nodular lymphoma, unspecified site, extranodal solid organ sites
A Phase II, Single Arm, Multicenter Open Label Trial to Determine the Efficacy and Safety of Tisagenlecleucel (CTL019) in Adult Patients With Refractory or Relapsed Follicular Lymphoma
-
Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/03/01
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Refractory or Relapsed Follicular Lymphoma
Objectives
Primary
Evaluate the efficacy of tisagenlecleucel therapy as measured by CRR determined by IRC
Complete response rate (CRR) determined by an Independent Review Committee (IRC) in the efficacy
analysis set (EAS) based on Lugano 2014 classification response criteria
Other Secondary
Evaluate the efficacy of tisagenlecleucel as measured by additional efficacy measures, including ORR, DOR, PFS and OS
Evaluate safety of tisagenlecleucel
Characterize the in vivo cellular kinetics (levels, expansion, persistence) of tisagenlecleucel transduced cells into target tissues (blood, bone marrow, and other tissues if available) and CD3+ tisagenlecleucel cells in peripheral blood, summarized by clinical response
Characterize the incidence and prevalence of tisagenlecleucel immunogenicity (humoral and cellular)
Characterize the impact of pre-existing and treatment induced immunogenicity (cellular and humoral) on cellular kinetics, efficacy and safety
Describe the effect of tisagenlecleucel therapy on Patient reported outcomes (PRO)
Test Drug
CTL019
Active Ingredient
tisagenlecleucel
Dosage Form
infusion
Dosage
0.6-6.0x10^8 CART-positive viable T cells, 30-70mL
Endpoints
Primary Outcome Measures :
Complete response rate (CRR) [ Time Frame: 2 years ]
CRR based on Lugano classification response criteria
Secondary Outcome Measures :
Overall response rate (ORR) [ Time Frame: 2 years ]
ORR, including complete response (CR) and partial response (PR)
Duration of response (DOR) [ Time Frame: 2 years ]
Time from achievement of CR or PR to relapse or death due to follicular lymphoma
Progression free survival (PFS) [ Time Frame: 2 years ]
Time from tisagenlecleucel infusion to first documented disease progression or death due to any cause
Overall survival (OS) [ Time Frame: 2 years ]
Time from tisagenlecleucel infusion to death due to any cause
tisagenlecleucel transgene concentration [ Time Frame: 2 years ]
Transgene concentration as detected by qPCR in target tissue
Cmax; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (% or copies/ µg)
Tmax; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The time to reach maximum (peak) peripheral blood or other body fluid drug concentration after single dose administration (days)
AUC0-28; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The AUC from time zero to day 28, in peripheral blood (%*days or days*copies/ µg)
AUC0-84d; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The AUC from time zero to day 84, in peripheral blood (%*days or days*copies/ µg)
T1/2; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood
Tlast; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The last observed measureable timepoint after dose administration
Summary of exposure of CD3+ tisagenlecleucel cells in peripheral blood [ Time Frame: 2 years ]
In vivo cellular kinetics of CD3+ tisagenlecleucel cells detected by flow cytometry
humoral immunogenicity [ Time Frame: 2 years ]
Antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.
cellular immunogenicity [ Time Frame: 2 years ]
Presence of T lymphocytes activated by the tisagenlecleucel protein
Summary scores of PRO measured by SF-36v2 quality of life questionnaire [ Time Frame: 2 years ]
Effect of tisagenlecleucel therapy on Patient reported outcomes
Summary scores of PRO measured by EQ-5D-3L quality of life questionnaire [ Time Frame: 2 years ]
Effect of tisagenlecleucel therapy on Patient reported outcomes
Summary scores of PRO measured by FACT-Lym quality of life questionnaire [ Time Frame: 2 years ]
Effect of tisagenlecleucel therapy on Patient reported outcomes
Complete response rate (CRR) [ Time Frame: 2 years ]
CRR based on Lugano classification response criteria
Secondary Outcome Measures :
Overall response rate (ORR) [ Time Frame: 2 years ]
ORR, including complete response (CR) and partial response (PR)
Duration of response (DOR) [ Time Frame: 2 years ]
Time from achievement of CR or PR to relapse or death due to follicular lymphoma
Progression free survival (PFS) [ Time Frame: 2 years ]
Time from tisagenlecleucel infusion to first documented disease progression or death due to any cause
Overall survival (OS) [ Time Frame: 2 years ]
Time from tisagenlecleucel infusion to death due to any cause
tisagenlecleucel transgene concentration [ Time Frame: 2 years ]
Transgene concentration as detected by qPCR in target tissue
Cmax; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (% or copies/ µg)
Tmax; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The time to reach maximum (peak) peripheral blood or other body fluid drug concentration after single dose administration (days)
AUC0-28; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The AUC from time zero to day 28, in peripheral blood (%*days or days*copies/ µg)
AUC0-84d; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The AUC from time zero to day 84, in peripheral blood (%*days or days*copies/ µg)
T1/2; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood
Tlast; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
The last observed measureable timepoint after dose administration
Summary of exposure of CD3+ tisagenlecleucel cells in peripheral blood [ Time Frame: 2 years ]
In vivo cellular kinetics of CD3+ tisagenlecleucel cells detected by flow cytometry
humoral immunogenicity [ Time Frame: 2 years ]
Antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.
cellular immunogenicity [ Time Frame: 2 years ]
Presence of T lymphocytes activated by the tisagenlecleucel protein
Summary scores of PRO measured by SF-36v2 quality of life questionnaire [ Time Frame: 2 years ]
Effect of tisagenlecleucel therapy on Patient reported outcomes
Summary scores of PRO measured by EQ-5D-3L quality of life questionnaire [ Time Frame: 2 years ]
Effect of tisagenlecleucel therapy on Patient reported outcomes
Summary scores of PRO measured by FACT-Lym quality of life questionnaire [ Time Frame: 2 years ]
Effect of tisagenlecleucel therapy on Patient reported outcomes
Inclution Criteria
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Written informed consent prior to any screening procedures
2. ≥18 years of age at the time of ICF signature
3. FL (Grade 1, 2, 3A) confirmed histologically by central pathology review before
tisagenlecleucel infusion.
Sufficient formalin-fixed paraffin-embedded (FFPE) tumor samples obtained for this study
with a corresponding pathology report must be submitted. If not clinically feasible, an
archival tumor biopsy from the most recent relapse may be submitted. However, in case of
clinical symptoms, abnormal laboratory tests, and radiological images suggesting histologic
transformation, a fresh biopsy will be required. Excisional biopsies should be submitted; if
not possible, a core needle biopsy is allowed. Fine needle aspiration (FNA) is not allowed.
4. FL meeting one of the following criteria:
Refractory to a second line or later line of systemic therapy (including an anti-CD20
antibody and an alkylating agent) or relapsed within 6 months after completion of a
second line or later line of systemic therapy
Relapsed during anti-CD20 antibody maintenance (following at least two lines of
therapies as above) or within 6 months after maintenance completion
Relapsed after autologous HSCT
NOTE: Previous treatment with other FL-targeting medications (e.g. PI3K inhibitors) is
allowed provided that patients recovered from all treatment-related adverse events.
5. Radiographically measurable disease at screening defined as:
At least one nodal lesion greater than 20 mm in the long axis, regardless of the length
of the short axis AND/OR
Extranodal lesions (outside lymph node or nodal mass, including liver and spleen)
greater than 10 mm in long AND short axis
For detailed information please refer to Appendix 1 Guidelines for efficacy evaluation in
lymphoma studies
6. ECOG performance status that is either 0 or 1 at screening
7. Patients must meet the following laboratory values without transfusion at screening:
Absolute neutrophil count (ANC) ≥ 1,000/mm3
(≥ 1×109/L)
Absolute lymphocyte count (ALC) > 300/mm3
(> 0.3×109
/L)
Absolute number of CD3+ T cells > 150/mm3 (> 0.15×109
/L)
Platelets ≥ 50 000/mm3 (≥ 50×109
/L)
Hemoglobin ≥ 8.0 g/dl (≥ 4.9 mmol/L)
A serum creatinine of ≤1.5 times ULN or eGFR ≥ 60 mL/min/1.73 m2
ALT/AST ≤ 5 times the ULN
Total bilirubin ≤ 1.5 times ULN (with the exception of patients with Gilbert’s
syndrome. Patients with Gilbert’s syndrome may be included if their total bilirubin is
≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN
8. Adequate pulmonary function defined as:
No or mild dyspnea (≤ Grade 1)
Oxygen saturation measured by pulse oximetry > 90% on room air
9. Must have a leukapheresis product of non-mobilized cells accepted for manufacturing
1. Written informed consent prior to any screening procedures
2. ≥18 years of age at the time of ICF signature
3. FL (Grade 1, 2, 3A) confirmed histologically by central pathology review before
tisagenlecleucel infusion.
Sufficient formalin-fixed paraffin-embedded (FFPE) tumor samples obtained for this study
with a corresponding pathology report must be submitted. If not clinically feasible, an
archival tumor biopsy from the most recent relapse may be submitted. However, in case of
clinical symptoms, abnormal laboratory tests, and radiological images suggesting histologic
transformation, a fresh biopsy will be required. Excisional biopsies should be submitted; if
not possible, a core needle biopsy is allowed. Fine needle aspiration (FNA) is not allowed.
4. FL meeting one of the following criteria:
Refractory to a second line or later line of systemic therapy (including an anti-CD20
antibody and an alkylating agent) or relapsed within 6 months after completion of a
second line or later line of systemic therapy
Relapsed during anti-CD20 antibody maintenance (following at least two lines of
therapies as above) or within 6 months after maintenance completion
Relapsed after autologous HSCT
NOTE: Previous treatment with other FL-targeting medications (e.g. PI3K inhibitors) is
allowed provided that patients recovered from all treatment-related adverse events.
5. Radiographically measurable disease at screening defined as:
At least one nodal lesion greater than 20 mm in the long axis, regardless of the length
of the short axis AND/OR
Extranodal lesions (outside lymph node or nodal mass, including liver and spleen)
greater than 10 mm in long AND short axis
For detailed information please refer to Appendix 1 Guidelines for efficacy evaluation in
lymphoma studies
6. ECOG performance status that is either 0 or 1 at screening
7. Patients must meet the following laboratory values without transfusion at screening:
Absolute neutrophil count (ANC) ≥ 1,000/mm3
(≥ 1×109/L)
Absolute lymphocyte count (ALC) > 300/mm3
(> 0.3×109
/L)
Absolute number of CD3+ T cells > 150/mm3 (> 0.15×109
/L)
Platelets ≥ 50 000/mm3 (≥ 50×109
/L)
Hemoglobin ≥ 8.0 g/dl (≥ 4.9 mmol/L)
A serum creatinine of ≤1.5 times ULN or eGFR ≥ 60 mL/min/1.73 m2
ALT/AST ≤ 5 times the ULN
Total bilirubin ≤ 1.5 times ULN (with the exception of patients with Gilbert’s
syndrome. Patients with Gilbert’s syndrome may be included if their total bilirubin is
≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN
8. Adequate pulmonary function defined as:
No or mild dyspnea (≤ Grade 1)
Oxygen saturation measured by pulse oximetry > 90% on room air
9. Must have a leukapheresis product of non-mobilized cells accepted for manufacturing
Exclusion Criteria
Patients eligible for this study must not meet any of the following criteria:
1. Evidence of histologic transformation
2. Follicular Lymphoma Grade 3B
3. Prior anti-CD19 therapy
4. Prior gene therapy
5. Prior adoptive T cell therapy
6. Prior allogeneic hematopoietic stem cell transplant
7. Active CNS involvement by malignancy
8. Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre
syndrome, Amyotrophic Lateral Sclerosis)
9. Investigational medicinal product within the last 30 days or five half-lives (whichever is
longer) prior to screening
10. Presence of active or prior hepatitis B or C as indicated by serology (for detailed criteria
see Appendix 2) Serology must be repeated, if the interval between testing prior to
lymphodepletion and tisagenlecleucel infusion exceeds 8 weeks
11. Presence of HIV antibody. Serology must be repeated, if the interval between testing
prior to lymphodepletion and tisagenlecleucel infusion exceeds 8 weeks
12. Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture
positive ≤ 72 hours prior to tisagenlecleucel infusion)
13. Cardiac or cardiac repolarization abnormality, including any of the following:
14. Previous or concurrent malignancy with the following exceptions:
a. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is
required prior to enrollment)
b. In situ carcinoma of the cervix or breast, treated curatively and without evidence of
recurrence for at least 3 years prior to enrollment
c. A primary malignancy which has been completely resected and in complete remission
for ≥ 3 years at the time of enrollment
15. Pregnant or nursing (lactating) women
16. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception while
taking study treatment and for at least 12 months after the tisagenlecleucel infusion and
until CAR T-cells are no longer present by qPCR on two consecutive tests.
17. Sexually active males must use a condom during intercourse while taking study treatment
and for at least12 months after the tisagenlecleucel infusion and until CAR T-cells are no
longer present by qPCR on two consecutive tests. A condom is required for all sexually
active male participants to prevent them from fathering a child AND to prevent delivery of
study treatment via seminal fluid to their partner. In addition, male participants must not
donate sperm for the time period specified above.
18. Intolerance to the excipients of the tisagenlecleucel cell product.
1. Evidence of histologic transformation
2. Follicular Lymphoma Grade 3B
3. Prior anti-CD19 therapy
4. Prior gene therapy
5. Prior adoptive T cell therapy
6. Prior allogeneic hematopoietic stem cell transplant
7. Active CNS involvement by malignancy
8. Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre
syndrome, Amyotrophic Lateral Sclerosis)
9. Investigational medicinal product within the last 30 days or five half-lives (whichever is
longer) prior to screening
10. Presence of active or prior hepatitis B or C as indicated by serology (for detailed criteria
see Appendix 2) Serology must be repeated, if the interval between testing prior to
lymphodepletion and tisagenlecleucel infusion exceeds 8 weeks
11. Presence of HIV antibody. Serology must be repeated, if the interval between testing
prior to lymphodepletion and tisagenlecleucel infusion exceeds 8 weeks
12. Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture
positive ≤ 72 hours prior to tisagenlecleucel infusion)
13. Cardiac or cardiac repolarization abnormality, including any of the following:
14. Previous or concurrent malignancy with the following exceptions:
a. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is
required prior to enrollment)
b. In situ carcinoma of the cervix or breast, treated curatively and without evidence of
recurrence for at least 3 years prior to enrollment
c. A primary malignancy which has been completely resected and in complete remission
for ≥ 3 years at the time of enrollment
15. Pregnant or nursing (lactating) women
16. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception while
taking study treatment and for at least 12 months after the tisagenlecleucel infusion and
until CAR T-cells are no longer present by qPCR on two consecutive tests.
17. Sexually active males must use a condom during intercourse while taking study treatment
and for at least12 months after the tisagenlecleucel infusion and until CAR T-cells are no
longer present by qPCR on two consecutive tests. A condom is required for all sexually
active male participants to prevent them from fathering a child AND to prevent delivery of
study treatment via seminal fluid to their partner. In addition, male participants must not
donate sperm for the time period specified above.
18. Intolerance to the excipients of the tisagenlecleucel cell product.
The Estimated Number of Participants
-
Taiwan
4 participants
-
Global
113 participants
