Anaplastic Large-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma
Conditions
Keywords
Antibodies, Monoclonal, Antibody-Drug Conjugate, Antigens, CD30, Drug Therapy, Hematologic Diseases, Lymphoma, Monomethyl auristatin E, Lymphoma, T-Cell, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic
Brief summary
This is a double-blind, randomized, multicenter, phase 3 clinical trial to compare the efficacy and safety of brentuximab vedotin in combination with CHP with the standard-of-care CHOP in patients with CD30-positive mature T-cell lymphomas.
Interventions
DRUGbrentuximab vedotin
1.8 mg/kg every 3 weeks by IV infusion for 6-8 cycles
DRUGdoxorubicin
50 mg/m2 every 3 weeks by IV infusion for 6-8 cycles
DRUGprednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for 6-8 cycles
DRUGvincristine
1.4 mg/m2 (maximum 2 mg) every 3 weeks by IV infusion for 6-8 cycles
DRUGcyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for 6-8 cycles
Sponsors
Millennium Pharmaceuticals, Inc.
Seagen Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with newly diagnosed, CD30-positive mature T-cell lymphomas * Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm by CT * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
Exclusion criteria
* History of another primary invasive malignancy that has not been in remission for at least 3 years * Current diagnosis of primary cutaneous CD30-positive T-cell lymphoproliferative disorders and lymphomas or mycosis fungoides * History of progressive multifocal leukoencephalopathy (PML) * Cerebral/meningeal disease related to the underlying malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Per Independent Review Facility (IRF) | Up to 60 months | The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) Rate Per IRF at End of Treatment (EOT) | Up to 8.34 months | The count of participants with CR per IRF following the completion of study treatment (at end of treatment or at the first assessment after the last dose of study treatment and prior to long-term follow-up) according to the Revised Response Criteria for Malignant Lymphoma. |
| Overall Survival (OS) | Up to 90 months | The time from randomization to death due to any cause. |
| Progression-free Survival Per IRF in Patients With Systemic Anaplastic Large Cell Lymphoma (sALCL) | Up to 60 months | The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first. |
| Incidence of Adverse Events (AEs) | Up to 8.28 months | Any untoward medical occurrence in a clinical investigational participant administered a medicinal product which does not necessarily have a causal relationship with this treatment. |
| Incidence of Laboratory Abnormalities | Up to 8.28 months | Number of participants who experienced a Grade 3 or higher laboratory toxicity. |
| Objective Response Rate (ORR) Per IRF at End of Treatment | Up to 8.34 months | The count of participants with CR or partial response (PR) per IRF following the completion of study treatment (at end of treatment or the first assessment after the last dose of study treatment and prior to long-term follow-up) according to the Revised Response Criteria for Malignant Lymphoma. |
Countries
Australia, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Poland, Romania, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Jan2013-Nov2016
Participants by arm
| Arm | Count |
|---|---|
| A+CHP brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone brentuximab vedotin: 1.8 mg/kg every 3 weeks by IV infusion for 6-8 cycles doxorubicin: 50 mg/m2 every 3 weeks by IV infusion for 6-8 cycles prednisone: 100 mg on Days 1 to 5 of each 3-week cycle, orally for 6-8 cycles cyclophosphamide: 750 mg/m2 every 3 weeks by IV infusion for 6-8 cycles | 226 |
| CHOP cyclophosphamide, doxorubicin, vincristine, and prednisone doxorubicin: 50 mg/m2 every 3 weeks by IV infusion for 6-8 cycles prednisone: 100 mg on Days 1 to 5 of each 3-week cycle, orally for 6-8 cycles vincristine: 1.4 mg/m2 (maximum 2 mg) every 3 weeks by IV infusion for 6-8 cycles cyclophosphamide: 750 mg/m2 every 3 weeks by IV infusion for 6-8 cycles | 226 |
| Total | 452 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Change of diagnosis | 1 | 0 |
| Overall Study | Death | 68 | 89 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | Not eligible, no study drug received | 1 | 0 |
| Overall Study | Withdrawal by Subject | 22 | 16 |
Baseline characteristics
| Characteristic | Total | A+CHP | CHOP |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 139 Participants | 69 Participants | 70 Participants |
| Age, Categorical Between 18 and 65 years | 313 Participants | 157 Participants | 156 Participants |
| Age, Continuous | 58 years | 58 years | 58 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 178 Participants | 85 Participants | 93 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 176 Participants | 90 Participants | 86 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2 | 98 Participants | 51 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 10 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 379 Participants | 186 Participants | 193 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 59 Participants | 30 Participants | 29 Participants |
| Race/Ethnicity, Customized Asian | 99 Participants | 45 Participants | 54 Participants |
| Race/Ethnicity, Customized Black or African American | 18 Participants | 12 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 48 Participants | 26 Participants | 22 Participants |
| Race/Ethnicity, Customized White | 281 Participants | 139 Participants | 142 Participants |
| Region of Enrollment Australia | 14 Participants | 6 Participants | 8 Participants |
| Region of Enrollment Canada | 6 Participants | 3 Participants | 3 Participants |
| Region of Enrollment Czechia | 22 Participants | 10 Participants | 12 Participants |
| Region of Enrollment Denmark | 14 Participants | 9 Participants | 5 Participants |
| Region of Enrollment France | 36 Participants | 18 Participants | 18 Participants |
| Region of Enrollment Germany | 27 Participants | 15 Participants | 12 Participants |
| Region of Enrollment Hungary | 9 Participants | 4 Participants | 5 Participants |
| Region of Enrollment Israel | 12 Participants | 8 Participants | 4 Participants |
| Region of Enrollment Italy | 37 Participants | 17 Participants | 20 Participants |
| Region of Enrollment Japan | 43 Participants | 20 Participants | 23 Participants |
| Region of Enrollment Poland | 7 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Romania | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment South Korea | 40 Participants | 17 Participants | 23 Participants |
| Region of Enrollment Spain | 26 Participants | 15 Participants | 11 Participants |
| Region of Enrollment Taiwan, Province Of China | 9 Participants | 5 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 21 Participants | 7 Participants | 14 Participants |
| Region of Enrollment United States | 127 Participants | 70 Participants | 57 Participants |
| Sex: Female, Male Female | 168 Participants | 93 Participants | 75 Participants |
| Sex: Female, Male Male | 284 Participants | 133 Participants | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 67 / 223 | 89 / 226 | 1 / 3 |
| other Total, other adverse events | 220 / 223 | 218 / 226 | 0 / 0 |
| serious Total, serious adverse events | 89 / 223 | 90 / 226 | 0 / 0 |
Outcome results
Primary
Progression-free Survival Per Independent Review Facility (IRF)
The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first.
Time frame: Up to 60 months
Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized patients. Patients are included in the treatment group assigned at randomization regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+CHP | Progression-free Survival Per Independent Review Facility (IRF) | 48.20 months |
| CHOP | Progression-free Survival Per Independent Review Facility (IRF) | 20.80 months |
Secondary
Complete Remission (CR) Rate Per IRF at End of Treatment (EOT)
The count of participants with CR per IRF following the completion of study treatment (at end of treatment or at the first assessment after the last dose of study treatment and prior to long-term follow-up) according to the Revised Response Criteria for Malignant Lymphoma.
Time frame: Up to 8.34 months
Population: The ITT Analysis Set includes all randomized patients. Patients are included in the treatment group assigned at randomization regardless of the actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A+CHP | Complete Remission (CR) Rate Per IRF at End of Treatment (EOT) | 153 Participants |
| CHOP | Complete Remission (CR) Rate Per IRF at End of Treatment (EOT) | 126 Participants |
Secondary
Incidence of Adverse Events (AEs)
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product which does not necessarily have a causal relationship with this treatment.
Time frame: Up to 8.28 months
Population: The Safety Analysis Set includes all patients who receive any amount of brentuximab vedotin or any component of CHOP. Treatment group will be determined using the actual treatment received, regardless of the randomization treatment assignment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A+CHP | Incidence of Adverse Events (AEs) | Blinded study treatment-related AE | 201 Participants |
| A+CHP | Incidence of Adverse Events (AEs) | CHP treatment-related SAE | 62 Participants |
| A+CHP | Incidence of Adverse Events (AEs) | Any serious adverse event (SAE) | 87 Participants |
| A+CHP | Incidence of Adverse Events (AEs) | Treatment discontinuations due to AE | 14 Participants |
| A+CHP | Incidence of Adverse Events (AEs) | CHP treatment-related AE | 198 Participants |
| A+CHP | Incidence of Adverse Events (AEs) | Treatment discontinuations due to blinded study treatment-related AE | 10 Participants |
| A+CHP | Incidence of Adverse Events (AEs) | Blinded study treatment-related SAE | 58 Participants |
| A+CHP | Incidence of Adverse Events (AEs) | Treatment discontinuations due to CHP treatment-related AE | 8 Participants |
| A+CHP | Incidence of Adverse Events (AEs) | Any treatment-emergent AE | 221 Participants |
| CHOP | Incidence of Adverse Events (AEs) | Treatment discontinuations due to CHP treatment-related AE | 7 Participants |
| CHOP | Incidence of Adverse Events (AEs) | Any treatment-emergent AE | 221 Participants |
| CHOP | Incidence of Adverse Events (AEs) | Blinded study treatment-related AE | 193 Participants |
| CHOP | Incidence of Adverse Events (AEs) | CHP treatment-related AE | 205 Participants |
| CHOP | Incidence of Adverse Events (AEs) | Any serious adverse event (SAE) | 87 Participants |
| CHOP | Incidence of Adverse Events (AEs) | Blinded study treatment-related SAE | 45 Participants |
| CHOP | Incidence of Adverse Events (AEs) | CHP treatment-related SAE | 53 Participants |
| CHOP | Incidence of Adverse Events (AEs) | Treatment discontinuations due to AE | 15 Participants |
| CHOP | Incidence of Adverse Events (AEs) | Treatment discontinuations due to blinded study treatment-related AE | 10 Participants |
Secondary
Incidence of Laboratory Abnormalities
Number of participants who experienced a Grade 3 or higher laboratory toxicity.
Time frame: Up to 8.28 months
Population: The Safety Analysis Set includes all patients who receive any amount of brentuximab vedotin or any component of CHOP. Treatment group will be determined using the actual treatment received, regardless of the randomization treatment assignment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A+CHP | Incidence of Laboratory Abnormalities | Glucose High | 8 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Urate High | 5 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Alanine Aminotransferase High | 3 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Any Hematology Test | 68 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Phosphate Low | 4 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Absolute Neutrophil Count Low | 17 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Alkaline Phosphatase High | 1 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Hemoglobin High | 1 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Potassium High | 0 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Hemoglobin Low | 9 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Any Chemistry Test | 25 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Leukocytes Low | 12 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Potassium Low | 3 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Lymphocytes High | 0 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Calcium Low | 1 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Lymphocytes Low | 52 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Sodium High | 1 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Neutrophils Low | 17 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Albumin Low | 2 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Platelets Low | 1 Participants |
| A+CHP | Incidence of Laboratory Abnormalities | Sodium Low | 4 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Platelets Low | 1 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Any Chemistry Test | 23 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Alanine Aminotransferase High | 1 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Albumin Low | 3 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Alkaline Phosphatase High | 0 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Calcium Low | 1 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Glucose High | 6 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Phosphate Low | 3 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Potassium High | 2 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Potassium Low | 2 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Sodium High | 0 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Sodium Low | 6 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Urate High | 2 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Any Hematology Test | 78 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Absolute Neutrophil Count Low | 19 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Hemoglobin High | 0 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Hemoglobin Low | 13 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Leukocytes Low | 21 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Lymphocytes High | 1 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Lymphocytes Low | 61 Participants |
| CHOP | Incidence of Laboratory Abnormalities | Neutrophils Low | 19 Participants |
Secondary
Objective Response Rate (ORR) Per IRF at End of Treatment
The count of participants with CR or partial response (PR) per IRF following the completion of study treatment (at end of treatment or the first assessment after the last dose of study treatment and prior to long-term follow-up) according to the Revised Response Criteria for Malignant Lymphoma.
Time frame: Up to 8.34 months
Population: The ITT Analysis Set includes all randomized patients. Patients are included in the treatment group assigned at randomization regardless of the actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| A+CHP | Objective Response Rate (ORR) Per IRF at End of Treatment | 188 Participants |
| CHOP | Objective Response Rate (ORR) Per IRF at End of Treatment | 163 Participants |
Secondary
Overall Survival (OS)
The time from randomization to death due to any cause.
Time frame: Up to 90 months
Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized patients. Patients are included in the treatment group assigned at randomization regardless of the actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+CHP | Overall Survival (OS) | NA Months |
| CHOP | Overall Survival (OS) | NA Months |
Secondary
Progression-free Survival Per IRF in Patients With Systemic Anaplastic Large Cell Lymphoma (sALCL)
The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first.
Time frame: Up to 60 months
Population: This analysis population includes only patients with systemic anaplastic large cell lymphoma (sALCL).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+CHP | Progression-free Survival Per IRF in Patients With Systemic Anaplastic Large Cell Lymphoma (sALCL) | 55.66 months |
| CHOP | Progression-free Survival Per IRF in Patients With Systemic Anaplastic Large Cell Lymphoma (sALCL) | 32.03 months |