Follicular Lymphoma
Conditions
Brief summary
To demonstrate that CT-P10 is similar to Rituxan in terms of efficacy as determined by overall response rate at 7 months
Interventions
BIOLOGICALCT-P10
375mg/m2, IV on day1 of 4 cycles in induction period, and 12 cycles in maintenance period.
BIOLOGICALRituxan
375mg/m2, IV on day1 of 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.
Sponsors
Celltrion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of low tumour burden, CD20+ follicular lymphoma * Ann Arbor Stage II, III or IV
Exclusion criteria
* Has receive rituximab * Allergies or hypersensitivity to murine, chimeric, human or humanised proteins * Previous treatment for NHL * Any malignancy * Current or recent treatment with any other investigational medicinal product or device * pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint - Overall Response Rate by 7 Months | During the Month 7 (up to Maintenance Cycle 3; Week 28) | ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed CR (CRu), or partial response (PR) by central review. Per 1999 IWG criteria, the disease status was assessed by using contrasted CT and/or MRI, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: \>75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: ≥50% decrease in SPD of target lesions and no evidence of disease progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Baseline, Induction Cycle 1 (predose, 1 hr postdose), Induction Cycle 2 to 4 (predose), EOT1/EOT2 (anytime), Maintenance Cycle 1 to 2 (predose, 1hr postdose) and Maintenance Cycle 3 (predose). | B-cell kinetics were demonstrated by median values of B-cell counts. Any values below the LLoQ were set as LLoQ which was 20 cells/μL. |
| Secondary PK Endpoints - Cmax | 1, 2, 3, 4, 12, 20 weeks (predose, 1 hr post dose), EOT1/EOT2 (anytime during the day) and 28 week (predose) | — |
| Secondary PK Endpoints - Ctrough | 1, 2, 3, 4, 12, 20 weeks (predose, 1 hr post dose), EOT1/EOT2 (anytime during the day) and 28 week (predose) | — |
| Secondary Efficacy Endpoint - ORR Over the Study Period | up to 27 months | ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed CR (CRu), or partial response (PR). Per 1999 IWG criteria, the disease status was assessed by using contrasted CT and/or MRI, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: \>75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: ≥50% decrease in SPD of target lesions and no evidence of disease progression. |
| Secondary Efficacy Endpoint - Overall Survival (OS) | Overall study period (median follow-up of 29.2 months) | Overall survival was defined as the interval between randomization and death from any cause. Locally reviewed data was used for the secondary efficacy analyses. |
| Secondary Efficacy Endpoint - Time-to Progression (TTP) | Overall study period (Baseline, Month 3, 7, 13, 19 27, and every 6 months thereafter). | Time to progression was defined as the interval between randomization and disease progression/relapse by IWG 1999 (at least a 50% increase of any single nodal after smallest decrease) or death as a result of lymphoma, whichever occurred first. Locally reviewed data was used for the secondary efficacy analyses. |
| Secondary Efficacy Endpoint - Progression-free Survival (PFS) | Overall study period (Baseline, Month 3, 7, 13, 19 27, and every 6 months thereafter). | PFS was defined as the interval between randomization and disease progression/relapse by IWG 1999 (at least a 50% increase of any single nodal after smallest decrease) or death from any cause, whichever occurred first. Locally reviewed data was used for the secondary efficacy analyses. |
Countries
South Korea
Participant flow
Pre-assignment details
A total of 402 participants were screened for the study. Of those, 144 participants failed screening and 258 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| CT-P10 CT-P10 375mg/m2, IV, 4 cycles in induction period and additional 12 cycles in maintenance period | 130 |
| Rituxan Rituxan, 375mg/m2, IV, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period. | 128 |
| Total | 258 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 1st Year of the Maintenance Period (MP1) | Adverse Event | 3 | 1 |
| 1st Year of the Maintenance Period (MP1) | Death | 0 | 1 |
| 1st Year of the Maintenance Period (MP1) | Lack of Efficacy | 6 | 9 |
| 1st Year of the Maintenance Period (MP1) | Lost to Follow-up | 0 | 1 |
| 1st Year of the Maintenance Period (MP1) | Physician Decision | 1 | 3 |
| 1st Year of the Maintenance Period (MP1) | Protocol Violation | 1 | 0 |
| 1st Year of the Maintenance Period (MP1) | Withdrawal by Subject | 1 | 0 |
| 2nd Year of the Maintenance Period (MP2) | Adverse Event | 3 | 0 |
| 2nd Year of the Maintenance Period (MP2) | Lack of Efficacy | 6 | 5 |
| 2nd Year of the Maintenance Period (MP2) | Withdrawal by Subject | 0 | 1 |
| Induction Study Period | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | CT-P10 | Rituxan | Total |
|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 12.68 | 57.7 years STANDARD_DEVIATION 11.53 | 57.7 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 10 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants | 116 Participants | 226 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Female | 64 Participants | 71 Participants | 135 Participants |
| Sex: Female, Male Male | 66 Participants | 57 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 130 | 3 / 128 |
| other Total, other adverse events | 93 / 130 | 86 / 128 |
| serious Total, serious adverse events | 14 / 130 | 14 / 128 |
Outcome results
Primary
Primary Efficacy Endpoint - Overall Response Rate by 7 Months
ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed CR (CRu), or partial response (PR) by central review. Per 1999 IWG criteria, the disease status was assessed by using contrasted CT and/or MRI, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: \>75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: ≥50% decrease in SPD of target lesions and no evidence of disease progression.
Time frame: During the Month 7 (up to Maintenance Cycle 3; Week 28)
Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CT-P10 | Primary Efficacy Endpoint - Overall Response Rate by 7 Months | 108 Participants |
| Rituxan | Primary Efficacy Endpoint - Overall Response Rate by 7 Months | 104 Participants |
90% CI: [-6.43, 10.2]
Secondary
Secondary Efficacy Endpoint - ORR Over the Study Period
ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed CR (CRu), or partial response (PR). Per 1999 IWG criteria, the disease status was assessed by using contrasted CT and/or MRI, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: \>75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: ≥50% decrease in SPD of target lesions and no evidence of disease progression.
Time frame: up to 27 months
Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CT-P10 | Secondary Efficacy Endpoint - ORR Over the Study Period | 109 Participants |
| Rituxan | Secondary Efficacy Endpoint - ORR Over the Study Period | 112 Participants |
Secondary
Secondary Efficacy Endpoint - Overall Survival (OS)
Overall survival was defined as the interval between randomization and death from any cause. Locally reviewed data was used for the secondary efficacy analyses.
Time frame: Overall study period (median follow-up of 29.2 months)
Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CT-P10 | Secondary Efficacy Endpoint - Overall Survival (OS) | 12 months | 0.98 Proportion of Participants |
| CT-P10 | Secondary Efficacy Endpoint - Overall Survival (OS) | 24 months | 0.98 Proportion of Participants |
| CT-P10 | Secondary Efficacy Endpoint - Overall Survival (OS) | 36 months | 0.98 Proportion of Participants |
| CT-P10 | Secondary Efficacy Endpoint - Overall Survival (OS) | 42 months | 0.98 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Overall Survival (OS) | 42 months | 0.97 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Overall Survival (OS) | 12 months | 0.98 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Overall Survival (OS) | 36 months | 0.97 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Overall Survival (OS) | 24 months | 0.98 Proportion of Participants |
Secondary
Secondary Efficacy Endpoint - Progression-free Survival (PFS)
PFS was defined as the interval between randomization and disease progression/relapse by IWG 1999 (at least a 50% increase of any single nodal after smallest decrease) or death from any cause, whichever occurred first. Locally reviewed data was used for the secondary efficacy analyses.
Time frame: Overall study period (Baseline, Month 3, 7, 13, 19 27, and every 6 months thereafter).
Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CT-P10 | Secondary Efficacy Endpoint - Progression-free Survival (PFS) | 12 months | 0.93 Proportion of Participants |
| CT-P10 | Secondary Efficacy Endpoint - Progression-free Survival (PFS) | 24 months | 0.88 Proportion of Participants |
| CT-P10 | Secondary Efficacy Endpoint - Progression-free Survival (PFS) | 36 months | 0.80 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Progression-free Survival (PFS) | 12 months | 0.89 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Progression-free Survival (PFS) | 24 months | 0.83 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Progression-free Survival (PFS) | 36 months | 0.68 Proportion of Participants |
Secondary
Secondary Efficacy Endpoint - Time-to Progression (TTP)
Time to progression was defined as the interval between randomization and disease progression/relapse by IWG 1999 (at least a 50% increase of any single nodal after smallest decrease) or death as a result of lymphoma, whichever occurred first. Locally reviewed data was used for the secondary efficacy analyses.
Time frame: Overall study period (Baseline, Month 3, 7, 13, 19 27, and every 6 months thereafter).
Population: The ITT population consisted of all patients enrolled and randomly assigned to receive a study drug, regardless of whether or not any study drug dosing was completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CT-P10 | Secondary Efficacy Endpoint - Time-to Progression (TTP) | 36 months | 0.82 Proportion of Participants |
| CT-P10 | Secondary Efficacy Endpoint - Time-to Progression (TTP) | 12 months | 0.94 Proportion of Participants |
| CT-P10 | Secondary Efficacy Endpoint - Time-to Progression (TTP) | 24 months | 0.89 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Time-to Progression (TTP) | 24 months | 0.84 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Time-to Progression (TTP) | 36 months | 0.68 Proportion of Participants |
| Rituxan | Secondary Efficacy Endpoint - Time-to Progression (TTP) | 12 months | 0.89 Proportion of Participants |
Secondary
Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery)
B-cell kinetics were demonstrated by median values of B-cell counts. Any values below the LLoQ were set as LLoQ which was 20 cells/μL.
Time frame: Baseline, Induction Cycle 1 (predose, 1 hr postdose), Induction Cycle 2 to 4 (predose), EOT1/EOT2 (anytime), Maintenance Cycle 1 to 2 (predose, 1hr postdose) and Maintenance Cycle 3 (predose).
Population: The PD population consisted of all patients who received at least 1 dose (full) of study drug and had at least 1 posttreatment PD result.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Induction Cycle 3 (predose) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 1 (predose) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Induction Cycle 2 (predose) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 1 (1hr after end of infusion) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Induction Cycle 4 (predose) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 2 (predose) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Induction Cycle 1 (1hr after end of infusion) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 2 (1hr after end of infusion) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | EOT1 (anytime) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 3 (predose) | 20.0 cells/uL |
| CT-P10 | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Baseline | 95.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 3 (predose) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Baseline | 120.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Induction Cycle 1 (1hr after end of infusion) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Induction Cycle 2 (predose) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Induction Cycle 3 (predose) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Induction Cycle 4 (predose) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | EOT1 (anytime) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 1 (predose) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 1 (1hr after end of infusion) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 2 (predose) | 20.0 cells/uL |
| Rituxan | Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | Maintenance Cycle 2 (1hr after end of infusion) | 20.0 cells/uL |
Secondary
Secondary PK Endpoints - Cmax
Time frame: 1, 2, 3, 4, 12, 20 weeks (predose, 1 hr post dose), EOT1/EOT2 (anytime during the day) and 28 week (predose)
Population: The PK population consisted of all patients who received at least 1 dose (full) of study drug and had at least 1 posttreatment PK result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CT-P10 | Secondary PK Endpoints - Cmax | Induction Cycle 2 | 283.35 μg/mL | Standard Deviation 53.84 |
| CT-P10 | Secondary PK Endpoints - Cmax | Induction Cycle 4 | 373.46 μg/mL | Standard Deviation 70.5 |
| CT-P10 | Secondary PK Endpoints - Cmax | Induction Cycle 1 | 212.86 μg/mL | Standard Deviation 50.64 |
| CT-P10 | Secondary PK Endpoints - Cmax | Maintenance Cycle 1 | 256.97 μg/mL | Standard Deviation 65.61 |
| CT-P10 | Secondary PK Endpoints - Cmax | Induction Cycle 3 | 327.32 μg/mL | Standard Deviation 71.05 |
| CT-P10 | Secondary PK Endpoints - Cmax | Maintenance Cycle 2 | 239.70 μg/mL | Standard Deviation 65.72 |
| Rituxan | Secondary PK Endpoints - Cmax | Maintenance Cycle 2 | 249.86 μg/mL | Standard Deviation 69.02 |
| Rituxan | Secondary PK Endpoints - Cmax | Induction Cycle 1 | 217.38 μg/mL | Standard Deviation 56.33 |
| Rituxan | Secondary PK Endpoints - Cmax | Induction Cycle 2 | 285.98 μg/mL | Standard Deviation 62.26 |
| Rituxan | Secondary PK Endpoints - Cmax | Induction Cycle 3 | 341.59 μg/mL | Standard Deviation 77.95 |
| Rituxan | Secondary PK Endpoints - Cmax | Induction Cycle 4 | 383.05 μg/mL | Standard Deviation 83.86 |
| Rituxan | Secondary PK Endpoints - Cmax | Maintenance Cycle 1 | 265.03 μg/mL | Standard Deviation 53.73 |
Secondary
Secondary PK Endpoints - Ctrough
Time frame: 1, 2, 3, 4, 12, 20 weeks (predose, 1 hr post dose), EOT1/EOT2 (anytime during the day) and 28 week (predose)
Population: The PK population consisted of all patients who received at least 1 dose (full) of study drug and had at least 1 posttreatment PK result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CT-P10 | Secondary PK Endpoints - Ctrough | Induction Cycle 1 | 64.66 μg/mL | Standard Deviation 24.88 |
| CT-P10 | Secondary PK Endpoints - Ctrough | Induction Cycle 2 | 113.23 μg/mL | Standard Deviation 34.6 |
| CT-P10 | Secondary PK Endpoints - Ctrough | Induction Cycle 3 | 149.53 μg/mL | Standard Deviation 43.65 |
| CT-P10 | Secondary PK Endpoints - Ctrough | Induction Cycle 4 | 34.78 μg/mL | Standard Deviation 33.58 |
| CT-P10 | Secondary PK Endpoints - Ctrough | Maintenance Cycle 1 | 22.68 μg/mL | Standard Deviation 37.22 |
| CT-P10 | Secondary PK Endpoints - Ctrough | Maintenance Cycle 2 | 16.96 μg/mL | Standard Deviation 9.61 |
| Rituxan | Secondary PK Endpoints - Ctrough | Maintenance Cycle 1 | 21.35 μg/mL | Standard Deviation 20.9 |
| Rituxan | Secondary PK Endpoints - Ctrough | Induction Cycle 1 | 72.94 μg/mL | Standard Deviation 40.39 |
| Rituxan | Secondary PK Endpoints - Ctrough | Induction Cycle 4 | 31.38 μg/mL | Standard Deviation 19.15 |
| Rituxan | Secondary PK Endpoints - Ctrough | Induction Cycle 2 | 120.92 μg/mL | Standard Deviation 36.02 |
| Rituxan | Secondary PK Endpoints - Ctrough | Maintenance Cycle 2 | 18.37 μg/mL | Standard Deviation 10.86 |
| Rituxan | Secondary PK Endpoints - Ctrough | Induction Cycle 3 | 161.80 μg/mL | Standard Deviation 43.91 |