Lymphoma
Conditions
Keywords
Lymphoma, Anaplastic Large-cell, Relapsed, Refractory, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic, monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases
Brief summary
The purpose of this study is to assess the antitumor efficacy of single-agent brentuximab vedotin 1.8 mg/kg administered intravenously (IV) every 3 weeks, as measured by the overall objective response rate (ORR) in patients with r/r sALCL following at least 1 multiagent chemotherapy regimen (cyclophosphamide, doxorubicin hydrochloride \[hydroxydaunorubicin\], vincristine sulfate \[Oncovin\], and prednisone \[CHOP\] or equivalent multiagent chemotherapy regimens with curative intent).
Interventions
DRUGBrentuximab vedotin
Brentuximab vedotin IV infusion
Sponsors
Takeda Development Center Americas, Inc.
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants age 18 years or older, with relapsed or refractory sALCL who have previously received at least 1 multiagent chemotherapy * Bidimensional measurable disease * An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug, or agree to practice true abstinence * Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence * Clinical laboratory values as specified in the study protocol
Exclusion criteria
* Previous treatment with brentuximab vedotin. * Previously received an allogeneic transplant. * Participants with current diagnosis of primary cutaneous anaplastic large cell lymphoma \[ALCL\] (participants whose ALCL has transformed to sALCL are eligible). * Known cerebral/meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy (PML) * Female participants who are lactating and breastfeeding or pregnant * Known human immunodeficiency virus (HIV) positive * Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to data cut-off date: 04 May 2021 (Up to approximately 7 years) | ORR was defined as the percentage of participants with a complete remission (CR) or partial remission (PR) by Independent Review Facility (IRF) response assessment according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Per IRF | Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years) | PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. PFS per IRF is based upon the radiological assessment from an independent review facility. |
| Complete Remission Rate (CRR) Per IRF | Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years) | CRR is defined as percentage of participants with CR. CR is defined as the disappearance of all evidence of disease. |
| Overall Survival (OS) | Until disease progression, death, or end of study (Up to approximately 10.7 years) | OS is defined as the time from start of study treatment to date of death due to any cause. |
| Percentage of Participants Receiving Hematopoietic Stem Cell Transplant (SCT) Following Treatment With Brentuximab Vedotin | Until disease progression, death, or end of study (Up to approximately 10.7 years) | — |
| Duration of Response (DOR) Per IRF | Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years) | DOR was defined as the time between initial response and documented tumor progression in the subset of participants who achieved an objective response, either CR or PR. DOR per IRF was based upon the radiological assessment of measured lesions from an independent review facility. DOR was censored on the date of the last disease assessment documenting absence of progressive disease (PD) for participants who were lost to follow-up, withdrew consent, started a new anticancer therapy other than stem cell transplant (SCT), or discontinued treatment due to undocumented PD after the last adequate disease assessment. |
| Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion | Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion | — |
| Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody | Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion | — |
| Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE) | Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion | — |
| Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antibodies (NAb) to Brentuximab Vedotin | Up to 16 cycles (each cycle = 21 days) | — |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs by Severity (Grade 3 or Higher) | From first dose up to 30 days post last dose of study drug (Up to approximately 1 year) | An adverse event (AE): any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to medicinal product. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. Serious TEAEs: defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is a medically important event. |
Countries
Belgium, Croatia, Czechia, Hungary, Poland, Portugal, Romania, Spain, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
Participants took part in the study at various investigative sites globally from 23 January 2014 to 29 August 2024.
Pre-assignment details
Participants with a diagnosis of relapsed or refractory systemic anaplastic large cell lymphoma were enrolled to receive brentuximab vedotin 1.8 milligrams per kilogram (mg/kg).
Participants by arm
| Arm | Count |
|---|---|
| Brentuximab Vedotin 1.8 mg/kg Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute IV infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 25 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Reason Not Specified | 1 |
| Overall Study | Withdrawal by Subject | 3 |
| Overall Study | Withdrawal of Informed Consent | 1 |
Baseline characteristics
| Characteristic | Brentuximab Vedotin 1.8 mg/kg |
|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 16.7 |
| Body Mass Index (BMI) | 26.9 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 6.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Height | 166.8 centimeters (cm) STANDARD_DEVIATION 10.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 50 Participants |
| Region of Enrollment Belgium | 1 Participants |
| Region of Enrollment Croatia | 2 Participants |
| Region of Enrollment Czech Republic | 12 Participants |
| Region of Enrollment Hungary | 5 Participants |
| Region of Enrollment Poland | 8 Participants |
| Region of Enrollment Portugal | 3 Participants |
| Region of Enrollment Romania | 3 Participants |
| Region of Enrollment Spain | 4 Participants |
| Region of Enrollment Turkey | 6 Participants |
| Region of Enrollment United Kingdom | 6 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 19 Participants |
| Weight | 75.2 kilograms (kg) STANDARD_DEVIATION 20.73 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 25 / 50 |
| other Total, other adverse events | 37 / 50 |
| serious Total, serious adverse events | 16 / 50 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a complete remission (CR) or partial remission (PR) by Independent Review Facility (IRF) response assessment according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
Time frame: Up to data cut-off date: 04 May 2021 (Up to approximately 7 years)
Population: Intent-to-Treat Population included all participants enrolled in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Objective Response Rate (ORR) | 64 percentage of participants |
Secondary
Complete Remission Rate (CRR) Per IRF
CRR is defined as percentage of participants with CR. CR is defined as the disappearance of all evidence of disease.
Time frame: Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
Population: Intent-to-Treat Population included all participants enrolled in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Complete Remission Rate (CRR) Per IRF | 30 percentage of participants |
Secondary
Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion
Time frame: Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
Population: Pharmacokinetic (PK) Population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. Number analyzed are participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion | Cycle 1, Day 1 | 35 micrograms per liter (µg/L) | Geometric Coefficient of Variation 35 |
| Brentuximab Vedotin 1.8 mg/kg | Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion | Cycle 3, Day 1 | 38 micrograms per liter (µg/L) | Geometric Coefficient of Variation 25 |
Secondary
Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody
Time frame: Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
Population: PK Population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. Number analyzed are participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody | Cycle 1, Day 1 | 33 µg/L | Geometric Coefficient of Variation 29 |
| Brentuximab Vedotin 1.8 mg/kg | Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody | Cycle 3, Day 1 | 38 µg/L | Geometric Coefficient of Variation 23 |
Secondary
Duration of Response (DOR) Per IRF
DOR was defined as the time between initial response and documented tumor progression in the subset of participants who achieved an objective response, either CR or PR. DOR per IRF was based upon the radiological assessment of measured lesions from an independent review facility. DOR was censored on the date of the last disease assessment documenting absence of progressive disease (PD) for participants who were lost to follow-up, withdrew consent, started a new anticancer therapy other than stem cell transplant (SCT), or discontinued treatment due to undocumented PD after the last adequate disease assessment.
Time frame: Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
Population: Intent-to-Treat Population included all participants enrolled in the study. Only responders were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Duration of Response (DOR) Per IRF | NA months |
Secondary
Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE)
Time frame: Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion
Population: PK Population included participants who received at least 1 dose of brentuximab vedotin and have PK concentration data available. Number analyzed are participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE) | Cycle 1, Day 1 | 0.25 nanogram per milliliter (ng/ml) | Geometric Coefficient of Variation 87 |
| Brentuximab Vedotin 1.8 mg/kg | Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE) | Cycle 3, Day 1 | 0.29 nanogram per milliliter (ng/ml) | Geometric Coefficient of Variation 88 |
Secondary
Overall Survival (OS)
OS is defined as the time from start of study treatment to date of death due to any cause.
Time frame: Until disease progression, death, or end of study (Up to approximately 10.7 years)
Population: Intent-to-Treat Population included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Overall Survival (OS) | 67.6 months |
Secondary
Percentage of Participants Receiving Hematopoietic Stem Cell Transplant (SCT) Following Treatment With Brentuximab Vedotin
Time frame: Until disease progression, death, or end of study (Up to approximately 10.7 years)
Population: Intent-to-Treat Population included all participants enrolled in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Percentage of Participants Receiving Hematopoietic Stem Cell Transplant (SCT) Following Treatment With Brentuximab Vedotin | 28 percentage of participants |
Secondary
Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antibodies (NAb) to Brentuximab Vedotin
Time frame: Up to 16 cycles (each cycle = 21 days)
Population: Immunogenicity-evaluable Population included all participants who received at least 1 dose of brentuximab vedotin and had a baseline and at least 1 post-baseline sample available for evaluation for the presence of ATA and NAb. Overall number analyzed are participants with data available for analyses at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antibodies (NAb) to Brentuximab Vedotin | ATA Positive | 30 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg | Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antibodies (NAb) to Brentuximab Vedotin | Neutralizing ATA Positive | 0.0 percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs by Severity (Grade 3 or Higher)
An adverse event (AE): any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to medicinal product. TEAE was defined as any AE that started after the first administration of study drug in this continuation study. Serious TEAEs: defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is a medically important event.
Time frame: From first dose up to 30 days post last dose of study drug (Up to approximately 1 year)
Population: Safety Population included all participants who received at least 1 dose of brentuximab vedotin.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs by Severity (Grade 3 or Higher) | TEAEs | 94 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs by Severity (Grade 3 or Higher) | Serious TEAEs | 32 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs by Severity (Grade 3 or Higher) | Drug-Related TEAEs | 70 percentage of participants |
| Brentuximab Vedotin 1.8 mg/kg | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs by Severity (Grade 3 or Higher) | TEAEs by Severity (Grade 3 or Higher) | 58 percentage of participants |
Secondary
Progression-free Survival (PFS) Per IRF
PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. PFS per IRF is based upon the radiological assessment from an independent review facility.
Time frame: Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years)
Population: Intent-to-Treat Population included all participants enrolled in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Brentuximab Vedotin 1.8 mg/kg | Progression-free Survival (PFS) Per IRF | 20.9 months |