A Phase 3 Study of Brentuximab Vedotin (SGN-35) in Patients at High Risk of Residual Hodgkin Lymphoma Following Stem Cell Transplant (The AETHERA Trial)

Conditions

Disease, Hodgkin

Keywords

Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Disease, Hodgkin, Drug Therapy, Hematologic Diseases, Immunotherapy, Lymphoma, Monomethylauristatin E

Brief summary

This is a randomized, double-blind, placebo-controlled, multicenter phase 3 trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) and best supportive care (BSC) compared to placebo and BSC in treatment of residual Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT).

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Interventions

DRUGbrentuximab vedotin

Every 21 days by IV infusion (1.8 mg/kg)

DRUGplacebo

Every 21 days by IV infusion

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

* Patients with HL who have received ASCT in the previous 30-45 days * Patients at high risk of residual HL post ASCT * Histologically-confirmed HL * ECOG of 0 or 1 * Adequate organ function

Exclusion criteria

* Previous treatment with brentuximab vedotin * Previously received an allogeneic transplant * Patients who were determined to have a best clinical response of progressive disease with salvage treatment immediately prior to ASCT * History of another primary malignancy that has not been in remission for at least 3 years * Post ASCT or current therapy with other systemic anti-neoplastic or investigational agents

Design outcomes

Primary

Measure	Time frame	Description
Progression-free Survival by Independent Review	Up to approximately 4 years	Time from date of randomization to the first documentation of disease progression by independent review or to death due to any cause, whichever comes first

Secondary

Measure	Time frame	Description
Overall Survival	Up to approximately 10 years	Time from date of randomization to date of death due to any cause
Incidence of Adverse Events or Laboratory Abnormalities	Up to 12 months	—
Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Up to 12 months	—

Countries

Bulgaria, Czechia, France, Germany, Hungary, Italy, Poland, Romania, Russia, Serbia, Spain, United Kingdom, United States

Participant flow

Recruitment details

Apr 2010-Aug 2014

Participants by arm

Arm	Count
Brentuximab Vedotin brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion	165
Placebo placebo every 3 weeks by IV infusion	164
Total	329

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	45	40
Overall Study	Lost to Follow-up	13	28
Overall Study	Site request to end participation in study	0	1
Overall Study	Withdrawal by Subject	18	25

Baseline characteristics

Characteristic	Brentuximab Vedotin	Placebo	Total
Age, Continuous	33 years	32 years	32 years
Best Response to Salvage Therapy pre-ASCT Complete remission	61 Participants	62 Participants	123 Participants
Best Response to Salvage Therapy pre-ASCT Partial remission	57 Participants	56 Participants	113 Participants
Best Response to Salvage Therapy pre-ASCT Stable disease	47 Participants	46 Participants	93 Participants
Eastern Cooperative Oncology Group Performance Status 0	87 Participants	97 Participants	184 Participants
Eastern Cooperative Oncology Group Performance Status 1	77 Participants	67 Participants	144 Participants
Eastern Cooperative Oncology Group Performance Status 2	1 Participants	0 Participants	1 Participants
Hodgkin Lymphoma Status after end of Frontline Therapy Refractory	99 Participants	97 Participants	196 Participants
Hodgkin Lymphoma Status after end of Frontline Therapy Relapse 12 months or later with extranodal disease	13 Participants	13 Participants	26 Participants
Hodgkin Lymphoma Status after end of Frontline Therapy Relapse in less than 12 months	53 Participants	54 Participants	107 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	3 Participants	5 Participants
Race (NIH/OMB) Black or African American	10 Participants	2 Participants	12 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	3 Participants	3 Participants
Race (NIH/OMB) White	153 Participants	156 Participants	309 Participants
Region of Enrollment Bulgaria	7 Participants	2 Participants	9 Participants
Region of Enrollment Czech Republic	5 Participants	0 Participants	5 Participants
Region of Enrollment France	8 Participants	5 Participants	13 Participants
Region of Enrollment Germany	0 Participants	3 Participants	3 Participants
Region of Enrollment Hungary	9 Participants	11 Participants	20 Participants
Region of Enrollment Italy	9 Participants	7 Participants	16 Participants
Region of Enrollment Poland	26 Participants	28 Participants	54 Participants
Region of Enrollment Romania	4 Participants	6 Participants	10 Participants
Region of Enrollment Russian Federation	20 Participants	19 Participants	39 Participants
Region of Enrollment Serbia	3 Participants	6 Participants	9 Participants
Region of Enrollment Spain	4 Participants	6 Participants	10 Participants
Region of Enrollment United Kingdom	3 Participants	3 Participants	6 Participants
Region of Enrollment United States	67 Participants	68 Participants	135 Participants
Sex: Female, Male Female	89 Participants	67 Participants	156 Participants
Sex: Female, Male Male	76 Participants	97 Participants	173 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	40 / 160	45 / 167
other Total, other adverse events	127 / 160	151 / 167
serious Total, serious adverse events	21 / 160	43 / 167

Outcome results

Primary

Progression-free Survival by Independent Review

Time from date of randomization to the first documentation of disease progression by independent review or to death due to any cause, whichever comes first

Time frame: Up to approximately 4 years

Population: Intention-to-Treat analysis set

Arm	Measure	Value (MEDIAN)
Brentuximab Vedotin	Progression-free Survival by Independent Review	42.9 months
Placebo	Progression-free Survival by Independent Review	24.1 months

p-value: 0.00195% CI: [0.4, 0.81]Log Rank

Secondary

Incidence of Adverse Events or Laboratory Abnormalities

Time frame: Up to 12 months

Population: Safety Analysis Set includes all patients who received at least 1 dose of brentuximab vedotin or only received placebo: 2 patients randomized to placebo received a single dose of brentuximab vedotin and are included in the brentuximab vedotin arm; 2 patients randomized to placebo received no study treatment and are not included in the analysis

Arm	Measure	Group	Value (NUMBER)
Brentuximab Vedotin	Incidence of Adverse Events or Laboratory Abnormalities	Any Adverse Event with Severity >= Grade 3	93 participants
Brentuximab Vedotin	Incidence of Adverse Events or Laboratory Abnormalities	Any Treatment-Related Serious Adverse Events	19 participants
Brentuximab Vedotin	Incidence of Adverse Events or Laboratory Abnormalities	Any Treatment-Related Adverse Event	147 participants
Brentuximab Vedotin	Incidence of Adverse Events or Laboratory Abnormalities	Treatment Discontinuation Due to Adverse Event	54 participants
Brentuximab Vedotin	Incidence of Adverse Events or Laboratory Abnormalities	Any Serious Adverse Event	41 participants
Brentuximab Vedotin	Incidence of Adverse Events or Laboratory Abnormalities	Any Laboratory Abnormalities Severity >=Grade 3	69 participants
Brentuximab Vedotin	Incidence of Adverse Events or Laboratory Abnormalities	Any Treatment-Emergent Adverse Event	163 participants
Placebo	Incidence of Adverse Events or Laboratory Abnormalities	Any Laboratory Abnormalities Severity >=Grade 3	29 participants
Placebo	Incidence of Adverse Events or Laboratory Abnormalities	Any Treatment-Emergent Adverse Event	142 participants
Placebo	Incidence of Adverse Events or Laboratory Abnormalities	Any Treatment-Related Adverse Event	79 participants
Placebo	Incidence of Adverse Events or Laboratory Abnormalities	Any Adverse Event with Severity >= Grade 3	51 participants
Placebo	Incidence of Adverse Events or Laboratory Abnormalities	Any Serious Adverse Event	20 participants
Placebo	Incidence of Adverse Events or Laboratory Abnormalities	Any Treatment-Related Serious Adverse Events	7 participants
Placebo	Incidence of Adverse Events or Laboratory Abnormalities	Treatment Discontinuation Due to Adverse Event	10 participants

Secondary

Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin

Time frame: Up to 12 months

Population: ATA-evaluable patients (patients with a baseline and at least 1 postbaseline sample)

Arm	Measure	Group	Value (NUMBER)
Brentuximab Vedotin	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Positive: Transiently +'ve Postbaseline	9 participants
Brentuximab Vedotin	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Positive: Persistently +'ve Postbaseline	3 participants
Brentuximab Vedotin	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Negative	138 participants
Brentuximab Vedotin	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Negative: -'ve Postbaseline	92 participants
Brentuximab Vedotin	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Negative: Transiently +'ve Postbaseline	36 participants
Brentuximab Vedotin	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Negative: Persistently +'ve Postbaseline	10 participants
Brentuximab Vedotin	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Positive	19 participants
Brentuximab Vedotin	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Positive: -'ve Postbaseline	7 participants
Placebo	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Positive: -'ve Postbaseline	0 participants
Placebo	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Positive: Transiently +'ve Postbaseline	5 participants
Placebo	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Negative: Transiently +'ve Postbaseline	27 participants
Placebo	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Positive: Persistently +'ve Postbaseline	7 participants
Placebo	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Negative	142 participants
Placebo	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Positive	12 participants
Placebo	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Negative: Persistently +'ve Postbaseline	11 participants
Placebo	Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin	Baseline Negative: -'ve Postbaseline	104 participants

Secondary

Overall Survival

Time from date of randomization to date of death due to any cause

Time frame: Up to approximately 10 years

Population: Intention-to-Treat analysis set

Arm	Measure	Value (MEDIAN)
Brentuximab Vedotin	Overall Survival	NA months
Placebo	Overall Survival	NA months

A Phase 3 Study of Brentuximab Vedotin (SGN-35) in Patients at High Risk of Residual Hodgkin Lymphoma Following Stem Cell Transplant (The AETHERA Trial)

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Progression-free Survival by Independent Review

Incidence of Adverse Events or Laboratory Abnormalities

Incidence of Anti-therapeutic Antibodies (ATA) to Brentuximab Vedotin

Overall Survival