Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory (r/r) Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01492088
Collaborator
(none)
36
18
2
71.9
2
0
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety and pharmacokinetics, and determine the pediatric maximum tolerated dose and/or or recommended phase 2 dose of brentuximab vedotin.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat children who have relapsed or refractory (r/r) anaplastic large-cell lymphoma (sALCL) or Hodgkin lymphoma (HL). This study will look at the maximum tolerated dose and/or recommended phase 2 dose, safety and pharmacokinetics of brentuximab vedotin along with overall response of people who took brentuximab vedotin.
The study enrolled 36 patients. In the phase 1 portion of the study, 12 participants were enrolled to receive brentuximab vedotin 1.4-1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity.
Once the maximum tolerated dose and/or recommended phase 2 dose and pharmacokinetics of brentuximab vedotin was reached, participants were enrolled by diagnosis into two phase 2 study arms: relapsed or refractory sALCL or relapsed or refractory HL and received brentuximab vedotin 1.8 mg/kg as 30-minute IV on Day 1 of every 21-day cycle for up to 16 cycles. One participant received a maximum of 20 cycles at the joint discretion of the sponsor and the investigator for continued clinical benefit.
This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 5 years. Participants made multiple visits to the clinic, and were contacted by telephone every 12 weeks for 12 months after the end of treatment (EOT) for progression free survival and then every 6 months until death, study closure, or 2 years after enrollment of the last participant for overall survival.
Study Design
Study Type:
Interventional
Actual Enrollment
:
36 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of Brentuximab Vedotin (SGN-35) in Pediatric Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
Actual Study Start Date
:
Apr 16, 2012
Actual Primary Completion Date
:
Oct 12, 2016
Actual Study Completion Date
:
Apr 12, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Brentuximab vedotin: Phase 1 Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. Dose was escalated up to 1.8 mg/kg using a 3 + 3 dose escalation design to determine a maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) depending upon the dose limiting toxicity (DLT). |
Drug: Brentuximab vedotin
Brentuximab vedotin IV infusion
Other Names:
|
| Experimental: Brentuximab vedotin: Phase 2 Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there is evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
Drug: Brentuximab vedotin
Brentuximab vedotin IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
- Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]
Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
- Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]
Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.
- Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]
Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
- Serum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]
Blood samples were collected and tested for conjugated and unconjugated antibodies.
- Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]
Blood samples were collected and tested for MMAE plasma concentrations.
- Overall Response Rate (ORR) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months)]
Overall response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using 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 Outcome Measures
- Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) [Baseline up to EOT (Up to 15 months)]
Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA and nATA development) using a laboratory test. ATA-positive samples were further characterized as transiently ATA positive (defined as 1 or 2 post-Baseline ATA-positive responses), persistently ATA positive (defined as more than 2 post-Baseline ATA positive responses), and nATA positive or negative.
- Overall Response Rate (ORR) (Phase 1) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)]
Overall response rate is defined as the percentage of participants with CR or PR as assessed by an IRF using 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 to Progression (TTP) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)]
TTP is defined as the time in months from first dose until the first subsequent documentation of objective tumor progression. Progressive disease (PD) is defined as any new lesion or increase by ≥50% of previously involved sites from nadir.
- Time to Response (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)]
Time to response is defined as the time in months from the first dose of study treatment until the date of the first assessment of confirmed CR or PR. as assessed by an IRF using 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.
- Duration of Response (DOR) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)]
DOR is defined as the time in months from the date of first documentation of a CR or PR to the date of first documentation of tumor progression or PD per IRF assessment according to IWG criteria or to death due to any cause, whichever comes first. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
- Event Free Survival (EFS) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)]
EFS is defined as the time in months from first dose until any cause of treatment failure: disease progression, premature discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
- Progression Free Survival (PFS) (Phase 1 and 2) [Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)]
PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
- Overall Survival (OS) (Phase 1 and 2) [Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrolment of the last participant (Up to 72 months)]
OS is the time in months from start of study treatment to date of death due to any cause.
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) [From the first dose through 30 days after the last dose of study medication (up to 15 months)]
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
- Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]
Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
- Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2) [From the first dose through 30 days after the last dose of study medication (Up to 15 months)]
Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.
- Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]
Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
- Serum Concentration of Total Antibodies (Conjugated and Unconjugated) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]
Blood samples were collected and tested for conjugated and unconjugated antibodies.
- Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) [Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose]
Blood samples were collected and tested for MMAE plasma concentrations.
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female participants aged 2 to <18 years (5 to <18 years for Hodgkin lymphoma [HL])
-
Diagnosis of systemic anaplastic large-cell lymphoma (sALCL), or HL for which standard, curative, life-prolonging, or palliative treatment does not exist or is no longer effective
-
Participants with sALCL must have documented anaplastic lymphoma kinase (ALK) status and must be beyond first remission or refractory to front-line chemotherapy
-
Participants diagnosed with any relapsed or refractory CD30+ hematologic malignancy (e.g., primary mediastinal B-cell lymphoma) may be included in phase 1 of the study
-
Participants with HL must be in their second of later relapse, have failed systemic chemotherapy either as induction therapy for advanced stage disease or salvage therapy, and were ineligible for, refused, or previously received a stem cell transplant
-
Performance score ≥ 60 from Lansky Play Performance Scale if ≤16 years
-
Negative pregnancy test
-
Fertile Participants must use 2 effective methods of contraception prior to and through 6 months after the last dose of the study drug
Exclusion Criteria:
-
Current diagnosis of primary cutaneous ALCL (those with systemic ALCL are eligible)
-
Received an allogeneic stem cell transplant <3 months prior to the first dose of study medication, or presence of polymerase chain reaction (PCR)-detectable cytomegalovirus (CMV) in any post-allogeneic transplant participant
-
Receiving immunosuppressive therapy
-
Receiving systemic therapy for chronic graft-versus-host disease (topical therapy is allowed)
-
Previous treatment with any anti-CD30 antibody
-
Therapeutic monoclonal antibody use within the longer of 6 weeks or 5 plasma half-lives
-
Systemic cardiac disease that would, in the opinion of the investigator or medical monitor, interfere with assessment of efficacy or safety of the drug
-
History of another primary malignancy not in remission for at least 3 years (the following are exempt from the 3-year limit: nonmelanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)
-
Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML
-
History of cirrhosis
-
Active systemic viral, bacterial, or fungal infection requiring antimicrobial, antiviral therapy or antifungal therapy within 2 weeks prior to the first dose of study drug (routine antimicrobial prophylaxis is acceptable)
-
Concurrent therapy with other anti-neoplastic or experimental agents
-
Systemic corticosteroid therapy <7 days prior to first dose of the study medication
-
Any serious underlying medical condition that, in the opinion of the investigator or medical monitor, would impair their ability to receive or tolerate the planned treatment
-
Known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation
-
Received nitrogen mustard agents, melphalan, or BCNU therapy within 6 weeks prior to the first study dose
-
Prior autologous hematopoietic stem cell infusion <4 weeks prior to first study dose
-
Grade 2 or greater unresolved toxicity from prior antineoplastic therapy
-
Grade 2 or greater peripheral neuropathy
-
Female participants who are both lactating and breastfeeding, or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug
-
Received local palliative radiation therapy <14 days prior to the first dose of study medication
-
Received radiation therapy to more than 25% of the bone marrow-containing spaces < 84 days prior to first dose of study medication
-
Received a strong or listed moderate inhibitor of CYP3A4 <2 weeks prior to first study dose
-
Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aurora | Colorado | United States | ||
| 2 | Kansas City | Missouri | United States | ||
| 3 | New York | New York | United States | ||
| 4 | Houston | Texas | United States | ||
| 5 | Bordeaux Cedex | France | |||
| 6 | Lyon | France | |||
| 7 | Paris Cedex 12 | France | |||
| 8 | Berlin | Germany | |||
| 9 | Frankfurt | Germany | |||
| 10 | Giessen | Germany | |||
| 11 | Halle | Germany | |||
| 12 | Munster | Germany | |||
| 13 | Padova | Italy | |||
| 14 | Roma | Italy | |||
| 15 | Mexico Df | Mexico | |||
| 16 | Rotterdam | Netherlands | |||
| 17 | Barcelona | Spain | |||
| 18 | London | United Kingdom |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01492088
Other Study ID Numbers:
- C25002
- 2011-001240-29
- U1111-1158-2613
- 133300410A0384
- NL38209.078.11
First Posted:
Dec 14, 2011
Last Update Posted:
Nov 20, 2018
Last Verified:
Nov 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Millennium Pharmaceuticals, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 12 investigative sites in United States, France, Germany, Netherlands, United Kingdom, Italy, Spain and Mexico from 16-April-2012 to 12-April-2018. |
|---|---|
| Pre-assignment Detail | Participants with diagnosis of relapsed or refractory (r/r) sALCL/HL were enrolled to receive brentuximab vedotin 1.4-1.8 mg/kg, intravenous infusion on Day 1 of every 21-day cycle for up to 16 cycles. Treatment beyond 16 cycles was permitted at joint discretion of sponsor and investigator for participants experiencing continued clinical benefit. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Period Title: Overall Study | |||
| STARTED | 3 | 16 | 17 |
| COMPLETED | 0 | 2 | 3 |
| NOT COMPLETED | 3 | 14 | 14 |
Baseline Characteristics
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | Total |
|---|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Total of all reporting groups |
| Overall Participants | 3 | 16 | 17 | 36 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
14.7
(1.15)
|
14.5
(2.68)
|
11.5
(3.18)
|
13.1
(3.19)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
1
33.3%
|
7
43.8%
|
3
17.6%
|
11
30.6%
|
| Male |
2
66.7%
|
9
56.3%
|
14
82.4%
|
25
69.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
4
23.5%
|
4
11.1%
|
| Not Hispanic or Latino |
3
100%
|
14
87.5%
|
12
70.6%
|
29
80.6%
|
| Unknown or Not Reported |
0
0%
|
2
12.5%
|
1
5.9%
|
3
8.3%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White |
2
66.7%
|
13
81.3%
|
16
94.1%
|
31
86.1%
|
| Asian |
1
33.3%
|
0
0%
|
1
5.9%
|
2
5.6%
|
| Other |
0
0%
|
2
12.5%
|
0
0%
|
2
5.6%
|
| Not Reported |
0
0%
|
1
6.3%
|
0
0%
|
1
2.8%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
2
66.7%
|
1
6.3%
|
1
5.9%
|
4
11.1%
|
| France |
0
0%
|
2
12.5%
|
0
0%
|
2
5.6%
|
| Germany |
0
0%
|
4
25%
|
1
5.9%
|
5
13.9%
|
| Netherlands |
0
0%
|
1
6.3%
|
2
11.8%
|
3
8.3%
|
| United Kingdom |
0
0%
|
1
6.3%
|
2
11.8%
|
3
8.3%
|
| Italy |
1
33.3%
|
7
43.8%
|
6
35.3%
|
14
38.9%
|
| Spain |
0
0%
|
0
0%
|
4
23.5%
|
4
11.1%
|
| Mexico |
0
0%
|
0
0%
|
1
5.9%
|
1
2.8%
|
| Height (cm) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [cm] |
167.17
(10.865)
|
165.31
(14.350)
|
149.54
(17.783)
|
158.02
(17.493)
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
53.10
(9.924)
|
57.85
(17.539)
|
42.16
(15.162)
|
50.04
(17.361)
|
| Body Surface Area (m^2) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [m^2] |
1.562
(0.0967)
|
1.617
(0.2938)
|
1.313
(0.3103)
|
1.469
(0.3228)
|
Outcome Measures
| Title | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) |
|---|---|
| Description | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. |
| Time Frame | From the first dose through 30 days after the last dose of study medication (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 9 |
| TEAE |
3
100%
|
9
56.3%
|
| SAE |
0
0%
|
4
25%
|
| Title | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1) |
|---|---|
| Description | Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention. |
| Time Frame | From the first dose through 30 days after the last dose of study medication (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 9 |
| Gamma-glutamyltransferase increased |
0
0%
|
1
6.3%
|
| Transaminases increased |
0
0%
|
1
6.3%
|
| Lymphocyte count decreased |
1
33.3%
|
1
6.3%
|
| Neutrophil count decreased |
0
0%
|
1
6.3%
|
| Blood bicarbonate decreased |
0
0%
|
1
6.3%
|
| Weight decreased |
0
0%
|
1
6.3%
|
| Hypocalaemia |
0
0%
|
2
12.5%
|
| Hyperuricaemia |
0
0%
|
1
6.3%
|
| Title | Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1) |
|---|---|
| Description | Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature. |
| Time Frame | From the first dose through 30 days after the last dose of study medication (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. Participants enrolled in Phase 1 of study were evaluated for this outcome measure. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 9 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1) |
|---|---|
| Description | Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate. |
| Time Frame | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 19. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 0 | 0 |
| Title | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1) |
|---|---|
| Description | Blood samples were collected and tested for conjugated and unconjugated antibodies. |
| Time Frame | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 20. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 0 | 0 |
| Title | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1) |
|---|---|
| Description | Blood samples were collected and tested for MMAE plasma concentrations. |
| Time Frame | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for this outcome measure was not summarized for Phase 1 participants only, data was summarized together for Phase 1 and 2 participants in brentuximab 1.4 mg/kg and 1.8 mg/kg arms groups. Data has been presented in OM 21. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 0 | 0 |
| Title | Overall Response Rate (ORR) (Phase 1 and 2) |
|---|---|
| Description | Overall response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using 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 | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r Hodgkin Lymphoma (HL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 15 | 17 |
| Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
47
293.8%
|
53
311.8%
|
| Title | Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) |
|---|---|
| Description | Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA and nATA development) using a laboratory test. ATA-positive samples were further characterized as transiently ATA positive (defined as 1 or 2 post-Baseline ATA-positive responses), persistently ATA positive (defined as more than 2 post-Baseline ATA positive responses), and nATA positive or negative. |
| Time Frame | Baseline up to EOT (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the Safety Population, all enrolled participants who received at least one dose of brentuximab vedotin, with data available for analysis. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 16 | 17 |
| ATA status: Transiently positive |
1
33.3%
|
4
25%
|
7
41.2%
|
| ATA status: Persistently positive |
0
0%
|
2
12.5%
|
0
0%
|
| nATA status: Positive |
0
0%
|
5
31.3%
|
4
23.5%
|
| Title | Overall Response Rate (ORR) (Phase 1) |
|---|---|
| Description | Overall response rate is defined as the percentage of participants with CR or PR as assessed by an IRF using 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 | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Participants enrolled in Phase 1 of the study were evaluated for this outcome measure. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle starting from Cycle 2 until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 8 |
| Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
63
393.8%
|
| Title | Time to Progression (TTP) (Phase 1 and 2) |
|---|---|
| Description | TTP is defined as the time in months from first dose until the first subsequent documentation of objective tumor progression. Progressive disease (PD) is defined as any new lesion or increase by ≥50% of previously involved sites from nadir. |
| Time Frame | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. TTP was censored on last radiological assessment of measured lesions documenting absence of PD for participants who did not have tumor progression. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 16 | 17 |
| Median (95% Confidence Interval) [months] |
2.7
|
4.8
|
6.2
|
| Title | Time to Response (Phase 1 and 2) |
|---|---|
| Description | Time to response is defined as the time in months from the first dose of study treatment until the date of the first assessment of confirmed CR or PR. as assessed by an IRF using 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 | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response-evaluable population included participants who received at least 1 dose of study drug, have measurable disease at baseline, and 1 postbaseline disease assessment. Time to response was censored on the last radiological assessment of measured lesions documenting absence of CR or PR for participants who did not have CR or PR. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 15 | 17 |
| Median (95% Confidence Interval) [months] |
NA
|
2.7
|
1.5
|
| Title | Duration of Response (DOR) (Phase 1 and 2) |
|---|---|
| Description | DOR is defined as the time in months from the date of first documentation of a CR or PR to the date of first documentation of tumor progression or PD per IRF assessment according to IWG criteria or to death due to any cause, whichever comes first. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. |
| Time Frame | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with response from the Safety Population, all enrolled participants who received at least one dose of brentuximab vedotin, with data available for analysis. Duration of response was censored at last observation documenting absence of PD for participants who did not have tumor progression. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 0 | 7 | 9 |
| Median (95% Confidence Interval) [months] |
NA
|
30.3
|
| Title | Event Free Survival (EFS) (Phase 1 and 2) |
|---|---|
| Description | EFS is defined as the time in months from first dose until any cause of treatment failure: disease progression, premature discontinuation of treatment for any reason, or death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. |
| Time Frame | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. EFS was censored on the last follow-up date if none of the above events occur during the study. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 16 | 17 |
| Median (95% Confidence Interval) [months] |
2.7
|
2.1
|
4.8
|
| Title | Progression Free Survival (PFS) (Phase 1 and 2) |
|---|---|
| Description | PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first. PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. |
| Time Frame | Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. PFS was censored on the day following the date of last radiological assessment of measured lesions documenting absence of PD for participants who did not have tumor progression. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 16 | 17 |
| Median (95% Confidence Interval) [months] |
2.7
|
3.8
|
6.2
|
| Title | Overall Survival (OS) (Phase 1 and 2) |
|---|---|
| Description | OS is the time in months from start of study treatment to date of death due to any cause. |
| Time Frame | Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrolment of the last participant (Up to 72 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 16 | 17 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
NA
|
| Title | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1 and 2) |
|---|---|
| Description | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. |
| Time Frame | From the first dose through 30 days after the last dose of study medication (up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 16 | 17 |
| TEAEs |
3
100%
|
16
100%
|
17
100%
|
| SAEs |
0
0%
|
7
43.8%
|
1
5.9%
|
| Title | Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1 and 2) |
|---|---|
| Description | Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention. |
| Time Frame | From the first dose through 30 days after the last dose of study medication (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 16 | 17 |
| Gamma-glutamyltransferase increased |
0
0%
|
2
12.5%
|
0
0%
|
| Alanine aminotransferase increased |
0
0%
|
1
6.3%
|
0
0%
|
| Aspartate aminotransferase increased |
0
0%
|
1
6.3%
|
0
0%
|
| Transaminases increased |
0
0%
|
1
6.3%
|
0
0%
|
| Lymphocyte count decreased |
1
33.3%
|
0
0%
|
2
11.8%
|
| Neutrophil count decreased |
0
0%
|
0
0%
|
2
11.8%
|
| White blood cell count decreased |
0
0%
|
0
0%
|
1
5.9%
|
| Blood bicarbonate decreased |
0
0%
|
1
6.3%
|
0
0%
|
| Weight decreased |
0
0%
|
0
0%
|
1
5.9%
|
| C-reactive protein increased |
0
0%
|
1
6.3%
|
0
0%
|
| Blood alkaline phosphatase increased |
0
0%
|
1
6.3%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Vital Signs Reported as AEs (Phase 1 and 2) |
|---|---|
| Description | Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature. |
| Time Frame | From the first dose through 30 days after the last dose of study medication (Up to 15 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population is defined as all participants who received at least 1 dose of study drug. Data was summarized together for Phase 1 and 2 participants in brentuximab 1.8 mg/kg arm group. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only |
|---|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 16 | 17 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1 and 2) |
|---|---|
| Description | Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate. |
| Time Frame | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 33 |
| Cycle 1 Day 1, Pre-Dose |
NA
(NA)
|
|
| Cycle 1 Day 1, 5 Minutes Post-Dose |
23.1
(3.46)
|
31.8
(12.4)
|
| Cycle 1 Day 2, 24 Hours Post-Dose |
9.50
(1.73)
|
13.0
(5.34)
|
| Cycle 1 Day 3, 48 Hours Post-Dose |
5.67
(0.924)
|
12.0
(16.3)
|
| Cycle 1 Day 5, 96 Hours Post-Dose |
3.50
(1.41)
|
8.68
(13.4)
|
| Cycle 1 Day 14, 312 Hours Post-Dose |
0.844
(0.309)
|
2.19
(3.44)
|
| Cycle 2 Day 1, Pre-Dose |
0.149
(0.128)
|
0.395
(0.322)
|
| Cycle 2 Day 1, 5-minutes Post-Dose |
25.3
(7.56)
|
32.9
(9.80)
|
| Cycle 2 Day 2, 24 Hours Post-Dose |
8.80
(6.19)
|
10.4
(8.05)
|
| Cycle 2 Day 3, 48 Hours Post-Dose |
3.70
(1.95)
|
11.4
(16.8)
|
| Cycle 2 Day 5, 96 Hours Post-Dose |
2.04
(1.26)
|
9.61
(17.9)
|
| Cycle 3 Day 1, Pre-Dose |
0.116
(0.163)
|
0.491
(0.387)
|
| Cycle 3 Day 1, 5 minutes Post-Dose |
23.9
(2.83)
|
31.3
(9.79)
|
| Cycle 4 Day 1, Pre-dose |
0.218
(0.271)
|
0.691
(0.492)
|
| Cycle 4 Day 1, 5 minutes Post-Dose |
22.9
(4.60)
|
30.0
(12.2)
|
| Cycle 5 Day 1, Pre-Dose |
0.264
(0.321)
|
0.845
(0.564)
|
| Cycle 5 Day 1, 5 minutes Post-Dose |
22.5
(3.32)
|
30.6
(15.1)
|
| Cycle 6 Day 1, Pre-Dose |
0.312
(0.351)
|
1.06
(0.699)
|
| Cycle 6 Day 1, 5 minutes Post-Dose |
20.3
(4.38)
|
33.2
(16.1)
|
| Cycle 7 Day 1, Pre-Dose |
0.327
(0.337)
|
1.04
(0.618)
|
| Cycle 7 Day 1, 5 minutes Post-Dose |
17.9
(2.40)
|
32.3
(15.4)
|
| Cycle 8 Day 1, Pre-Dose |
1.25
(0.565)
|
|
| Cycle 8 Day 1, 5 minutes Post-Dose |
35.2
(10.5)
|
|
| Cycle 8 Day 2, 24 Hours Post-Dose |
14.0
(4.55)
|
|
| Cycle 8 Day 3, 48 Hours Post-Dose |
9.53
(2.96)
|
|
| Cycle 8 Day 5, 96 Hours Post-Dose |
6.44
(2.35)
|
|
| Cycle 8 Day 14, 312 Hours Post-Dose |
3.30
(4.63)
|
|
| Cycle 9 Day 1, Pre-Dose |
4.37
(11.7)
|
|
| Cycle 9 Day 1, 5 Minutes Post-Dose |
29.6
(11.3)
|
|
| Cycle 10 Day 1, Pre-Dose |
1.20
(0.455)
|
|
| Cycle 10 Day 1, 5 minutes Post-Dose |
35.7
(9.50)
|
|
| Cycle 11 Day 1, Pre-Dose |
1.84
(1.57)
|
|
| Cycle 11 Day 1, 5 minutes Post-Dose |
35.7
(10.8)
|
|
| Cycle 12 Day 1, Pre-Dose |
1.47
(0.665)
|
|
| Cycle 12 Day 1, 5 minutes Post-Dose |
40.0
(10.4)
|
|
| Cycle 13 Day 1, Pre-Dose |
6.28
(11.5)
|
|
| Cycle 13 Day 1, 5 minutes Post-Dose |
33.3
(16.1)
|
|
| Cycle 14 Day 1, Pre-Dose |
1.60
(0.600)
|
|
| Cycle 14 Day 1, 5 minutes Post-Dose |
37.0
(7.92)
|
|
| Cycle 15 Day 1, Pre-Dose |
1.48
(0.542)
|
|
| Cycle 15 Day 1, 5 minutes Post-Dose |
40.3
(10.6)
|
|
| Cycle 16 Day 1, Pre-Dose |
1.52
(0.361)
|
|
| Cycle 16 Day 1, 5 minutes Post-Dose |
41.5
(4.70)
|
| Title | Serum Concentration of Total Antibodies (Conjugated and Unconjugated) |
|---|---|
| Description | Blood samples were collected and tested for conjugated and unconjugated antibodies. |
| Time Frame | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 33 |
| Cycle 1 Day 1, Pre-Dose |
NA
(NA)
|
NA
(NA)
|
| Cycle 1 Day 1, 5 Minutes Post-Dose |
26.3
(2.29)
|
34.7
(13.4)
|
| Cycle 1 Day 2, 24 Hours Post-Dose |
16.7
(1.50)
|
25.0
(9.59)
|
| Cycle 1 Day 3, 48 Hours Post-Dose |
12.7
(3.13)
|
18.5
(7.57)
|
| Cycle 1 Day 5, 96 Hours Post-Dose |
8.63
(5.11)
|
11.8
(5.02)
|
| Cycle 1 Day 14, 312 Hours Post-Dose |
2.23
(0.833)
|
3.50
(1.70)
|
| Cycle 2 Day 1, Pre-Dose |
0.470
(0.459)
|
1.16
(0.825)
|
| Cycle 2 Day 1, 5-minutes Post-Dose |
26.9
(7.98)
|
35.6
(12.0)
|
| Cycle 2 Day 2, 24 Hours Post-Dose |
17.1
(10.4)
|
17.2
(7.93)
|
| Cycle 2 Day 3, 48 Hours Post-Dose |
9.60
(5.39)
|
16.0
(6.73)
|
| Cycle 2 Day 3, 96 Hours Post-Dose |
6.43
(3.69)
|
10.2
(5.16)
|
| Cycle 3 Day 1, Pre-Dose |
0.415
(0.586)
|
1.62
(1.07)
|
| Cycle 3 Day 1, 5 minutes Post-Dose |
30.0
(5.87)
|
38.2
(13.1)
|
| Cycle 4 Day 1, Pre-dose |
0.875
(1.03)
|
1.95
(1.26)
|
| Cycle 4 Day 1, 5 minutes Post-Dose |
29.6
(8.13)
|
37.1
(15.6)
|
| Cycle 5 Day 1, Pre-Dose |
0.844
(0.928)
|
2.45
(1.68)
|
| Cycle 5 Day 1, 5 minutes Post-Dose |
29.4
(3.04)
|
38.0
(18.8)
|
| Cycle 6 Day 1, Pre-Dose |
1.05
(1.20)
|
2.99
(1.81)
|
| Cycle 6 Day 1, 5 minutes Post-Dose |
29.4
(5.37)
|
39.8
(19.8)
|
| Cycle 7 Day 1, Pre-Dose |
0.995
(0.998)
|
2.92
(1.62)
|
| Cycle 7 Day 1, 5 minutes Post-Dose |
24.0
(2.69)
|
41.0
(21.2)
|
| Cycle 8 Day 1, Pre-Dose |
3.29
(1.14)
|
|
| Cycle 8 Day 1, 5 minutes Post-Dose |
41.4
(9.47)
|
|
| Cycle 8 Day 2, 24 Hours Post-Dose |
28.2
(6.38)
|
|
| Cycle 8 Day 3, 48 Hours Post-Dose |
22.9
(5.67)
|
|
| Cycle 8 Day 5, 96 Hours Post-Dose |
17.3
(4.93)
|
|
| Cycle 8 Day 14, 312 Hours Post-Dose |
5.74
(2.02)
|
|
| Cycle 9 Day 1, Pre-Dose |
6.30
(12.0)
|
|
| Cycle 9 Day 1, 5 Minutes Post-Dose |
35.1
(11.3)
|
|
| Cycle 10 Day 1, Pre-Dose |
3.48
(1.13)
|
|
| Cycle 10 Day 1, 5 minutes Post-Dose |
41.4
(8.63)
|
|
| Cycle 11 Day 1, Pre-Dose |
3.96
(2.24)
|
|
| Cycle 11 Day 1, 5 minutes Post-Dose |
42.8
(8.85)
|
|
| Cycle 12 Day 1, Pre-Dose |
3.47
(1.28)
|
|
| Cycle 12 Day 1, 5 minutes Post-Dose |
44.8
(10.3)
|
|
| Cycle 13 Day 1, Pre-Dose |
11.3
(17.1)
|
|
| Cycle 13 Day 1, 5 minutes Post-Dose |
NA
(NA)
|
40.3
(19.2)
|
| Cycle 14 Day 1, Pre-Dose |
3.97
(1.14)
|
|
| Cycle 14 Day 1, 5 minutes Post-Dose |
44.5
(7.05)
|
|
| Cycle 15 Day 1, Pre-Dose |
4.02
(1.40)
|
|
| Cycle 15 Day 1, 5 minutes Post-Dose |
49.7
(6.88)
|
|
| Cycle 16 Day 1, Pre-Dose |
4.60
(1.67)
|
|
| Cycle 16 Day 1, 5 minutes Post-Dose |
49.7
(7.61)
|
| Title | Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2) |
|---|---|
| Description | Blood samples were collected and tested for MMAE plasma concentrations. |
| Time Frame | Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK-evaluable population was defined as participants with sufficient dosing and PK data to reliably estimate PK parameters. Cycle 2 Day 2 values are collected in phase 1 participants only. Here, number analyzed is number of participants assessed at given time-point. Data summarized together for all participants in brentuximab vedotin 1.8 mg/kg arm. |
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 |
|---|---|---|
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. |
| Measure Participants | 3 | 33 |
| Cycle 1 Day 1, Pre-Dose |
NA
(NA)
|
NA
(NA)
|
| Cycle 1 Day 1, 5 Minutes Post-Dose |
0.416
(0.480)
|
0.368
(0.309)
|
| Cycle 1 Day 2, 24 Hours Post-Dose |
4.63
(3.20)
|
4.88
(3.55)
|
| Cycle 1 Day 3, 48 Hours Post-Dose |
4.20
(1.95)
|
5.36
(3.72)
|
| Cycle 1 Day 5, 96 Hours Post-Dose |
2.80
(0.300)
|
4.43
(3.04)
|
| Cycle 1 Day 14, 312 Hours Post-Dose |
0.196
(0.0641)
|
0.530
(0.552)
|
| Cycle 2 Day 1, Pre-Dose |
0.0647
(0.0358)
|
0.0739
(0.0640)
|
| Cycle 2 Day 1, 5-minutes Post-Dose |
0.556
(0.562)
|
0.478
(0.461)
|
| Cycle 2 Day 2, 24 Hours Post-Dose |
5.63
(5.72)
|
3.71
(3.94)
|
| Cycle 2 Day 3, 48 Hours Post-Dose |
4.60
(3.70)
|
3.86
(3.18)
|
| Cycle 2 Day 5, 96 Hours Post-Dose |
2.60
(1.04)
|
2.70
(1.69)
|
| Cycle 3 Day 1, Pre-Dose |
0.0250
(0.0354)
|
0.0650
(0.0590)
|
| Cycle 3 Day 1, 5 minutes Post-Dose |
0.216
(0.0361)
|
0.514
(0.684)
|
| Cycle 4 Day 1, Pre-dose |
0.0565
(0.00495)
|
0.0866
(0.0784)
|
| Cycle 4 Day 1, 5 minutes Post-Dose |
0.234
(0.0742)
|
0.376
(0.449)
|
| Cycle 5 Day 1, Pre-Dose |
0.0820
(NA)
|
0.0862
(0.0729)
|
| Cycle 5 Day 1, 5 minutes Post-Dose |
0.334
(0.0955)
|
0.301
(0.248)
|
| Cycle 6 Day 1, Pre-Dose |
0.0680
(0.0156)
|
0.0841
(0.0632)
|
| Cycle 6 Day 1, 5 minutes Post-Dose |
0.247
(0.00707)
|
0.450
(0.663)
|
| Cycle 7 Day 1, Pre-Dose |
0.104
(0.0389)
|
0.0830
(0.0578)
|
| Cycle 7 Day 1, 5 minutes Post-Dose |
0.326
(0.0361)
|
0.310
(0.282)
|
| Cycle 8 Day 1, Pre-Dose |
0.101
(0.934)
|
|
| Cycle 8 Day 1, 5 minutes Post-Dose |
0.295
(0.151)
|
|
| Cycle 8 Day 2, 24 Hours Post-Dose |
1.96
(1.31)
|
|
| Cycle 8 Day 3, 48 Hours Post-Dose |
1.91
(1.29)
|
|
| Cycle 8 Day 5, 96 Hours Post-Dose |
2.00
(1.05)
|
|
| Cycle 8 Day 14, 312 Hours Post-Dose |
0.325
(0.214)
|
|
| Cycle 9 Day 1, Pre-Dose |
0.0819
(0.0496)
|
|
| Cycle 9 Day 1, 5 Minutes Post-Dose |
0.218
(0.128)
|
|
| Cycle 10 Day 1, Pre-Dose |
0.727
(0.0517)
|
|
| Cycle 10 Day 1, 5 minutes Post-Dose |
0.204
(0.0982)
|
|
| Cycle 11 Day 1, Pre-Dose |
0.0763
(0.0368)
|
|
| Cycle 11 Day 1, 5 minutes Post-Dose |
0.255
(0.133)
|
|
| Cycle 12 Day 1, Pre-Dose |
0.105
(0.0983)
|
|
| Cycle 12 Day 1, 5 minutes Post-Dose |
0.252
(0.116)
|
|
| Cycle 13 Day 1, Pre-Dose |
0.110
(0.0629)
|
|
| Cycle 13 Day 1, 5 minutes Post-Dose |
0.244
(0.130)
|
|
| Cycle 14 Day 1, Pre-Dose |
0.109
(0.0529)
|
|
| Cycle 14 Day 1, 5 minutes Post-Dose |
0.320
(0.138)
|
|
| Cycle 15 Day 1, Pre-Dose |
0.0843
(0.0548)
|
|
| Cycle 15 Day 1, 5 minutes Post-Dose |
0.404
(0.192)
|
|
| Cycle 16 Day 1, Pre-Dose |
0.139
(0.0926)
|
|
| Cycle 16 Day 1, 5 minutes Post-Dose |
0.381
(0.277)
|
Adverse Events
| Time Frame | From the first dose through 30 days after the last dose of study medication (Up to 15 months) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. At the time of study completion, a total of 9 deaths were reported for the safety population, 1 on study death (death within 30 days of last dose) and 8 deaths during post-treatment follow up (PTFU). | |||||
| Arm/Group Title | Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | |||
| Arm/Group Description | Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. | Participants with r/r HL received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | Participants with r/r systemic anaplastic large-cell lymphoma (sALCL) received brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle until there was evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit. | |||
All Cause Mortality |
||||||
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 6/16 (37.5%) | 2/17 (11.8%) | |||
Serious Adverse Events |
||||||
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 7/16 (43.8%) | 1/17 (5.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Cardiac disorders | ||||||
| Supraventricular tachycardia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Cardiac arrest | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Gastrointestinal disorders | ||||||
| Vomiting | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| General disorders | ||||||
| Pyrexia | 0/3 (0%) | 1/16 (6.3%) | 1/17 (5.9%) | |||
| Myalgia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatotoxicity | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Immune system disorders | ||||||
| Anaphylactic reaction | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Infections and infestations | ||||||
| Pneumonia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Brentuximab Vedotin 1.4 mg/kg: Phase 1 | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r HL Only | Brentuximab Vedotin 1.8 mg/kg: Phase 1 and 2 r/r sALCL Only | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 16/16 (100%) | 17/17 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Neutropenia | 0/3 (0%) | 4/16 (25%) | 1/17 (5.9%) | |||
| Lymph node pain | 0/3 (0%) | 2/16 (12.5%) | 1/17 (5.9%) | |||
| Lymphadenopathy | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Anaemia | 0/3 (0%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Leukopenia | 0/3 (0%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Thrombocytopenia | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Sinus tachycardia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Tinnitus | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Eye disorders | ||||||
| Eye discharge | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 2/3 (66.7%) | 7/16 (43.8%) | 4/17 (23.5%) | |||
| Vomiting | 0/3 (0%) | 2/16 (12.5%) | 3/17 (17.6%) | |||
| Abdominal pain upper | 1/3 (33.3%) | 2/16 (12.5%) | 1/17 (5.9%) | |||
| Abdominal pain | 1/3 (33.3%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Gastrointestinal pain | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Diarrhoea | 0/3 (0%) | 2/16 (12.5%) | 3/17 (17.6%) | |||
| Constipation | 0/3 (0%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Gastrooesophageal reflux disease | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Gastritis | 0/3 (0%) | 1/16 (6.3%) | 1/17 (5.9%) | |||
| Toothache | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Dyspepsia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Gastrointestinal motility disorder | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Dysphagia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Odynophagia | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| General disorders | ||||||
| Pyrexia | 1/3 (33.3%) | 8/16 (50%) | 7/17 (41.2%) | |||
| Fatigue | 0/3 (0%) | 2/16 (12.5%) | 1/17 (5.9%) | |||
| Asthenia | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Feeling hot | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Oedema peripheral | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatotoxicity | 0/3 (0%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Hypertransaminasaemia | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Hepatic pain | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Infections and infestations | ||||||
| Rhinitis | 0/3 (0%) | 3/16 (18.8%) | 4/17 (23.5%) | |||
| Pharyngitis | 0/3 (0%) | 3/16 (18.8%) | 3/17 (17.6%) | |||
| Nasopharyngitis | 0/3 (0%) | 1/16 (6.3%) | 1/17 (5.9%) | |||
| Sinusitis | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Upper respiratory tract infection | 1/3 (33.3%) | 0/16 (0%) | 0/17 (0%) | |||
| Gingivitis | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Tooth abscess | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Clostridium difficile colitis | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Conjunctivitis | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Vulvovaginal mycotic infection | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Herpes zoster | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Influenza | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Respiratory syncytial virus infection | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Paronychia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Joint dislocation | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Muscle strain | 1/3 (33.3%) | 0/16 (0%) | 0/17 (0%) | |||
| Head injury | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Facial bones fracture | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Investigations | ||||||
| Gamma-glutamyltransferase increased | 0/3 (0%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Alanine aminotransferase increased | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Aspartate aminotransferase increased | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Transaminases increased | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Lymphocyte count decreased | 1/3 (33.3%) | 0/16 (0%) | 2/17 (11.8%) | |||
| Neutrophil count decreased | 0/3 (0%) | 0/16 (0%) | 2/17 (11.8%) | |||
| White blood cell count decreased | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Blood bicarbonate decreased | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Weight decreased | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| C-reactive protein increased | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Blood alkaline phosphatase increased | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/3 (0%) | 3/16 (18.8%) | 0/17 (0%) | |||
| Hypokalaemia | 0/3 (0%) | 2/16 (12.5%) | 1/17 (5.9%) | |||
| Hyperuricaemia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Hypophosphataemia | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Hypoalbuminaemia | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Pain in extremity | 0/3 (0%) | 2/16 (12.5%) | 1/17 (5.9%) | |||
| Musculoskeletal pain | 0/3 (0%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Back pain | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Neck pain | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Myalgia | 0/3 (0%) | 4/16 (25%) | 0/17 (0%) | |||
| Arthralgia | 1/3 (33.3%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Muscle spasms | 0/3 (0%) | 1/16 (6.3%) | 1/17 (5.9%) | |||
| Groin pain | 0/3 (0%) | 1/16 (6.3%) | 1/17 (5.9%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Cancer pain | 1/3 (33.3%) | 0/16 (0%) | 0/17 (0%) | |||
| Nervous system disorders | ||||||
| Paraesthesia | 1/3 (33.3%) | 5/16 (31.3%) | 1/17 (5.9%) | |||
| Peripheral sensory neuropathy | 0/3 (0%) | 2/16 (12.5%) | 2/17 (11.8%) | |||
| Neuropathy peripheral | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Peripheral motor neuropathy | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Headache | 0/3 (0%) | 0/16 (0%) | 3/17 (17.6%) | |||
| Migraine | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Dysgeusia | 1/3 (33.3%) | 0/16 (0%) | 0/17 (0%) | |||
| Tremor | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Vocal cord paralysis | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 0/3 (0%) | 1/16 (6.3%) | 1/17 (5.9%) | |||
| Anxiety | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Renal and urinary disorders | ||||||
| Pollakiuria | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Urinary tract pain | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Menstruation irregular | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/3 (0%) | 3/16 (18.8%) | 1/17 (5.9%) | |||
| Oropharyngeal pain | 0/3 (0%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Dyspnoea | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 0/3 (0%) | 1/16 (6.3%) | 1/17 (5.9%) | |||
| Rash maculo-papular | 0/3 (0%) | 0/16 (0%) | 2/17 (11.8%) | |||
| Blister | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Dermatosis | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Dry skin | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Pruritus | 0/3 (0%) | 2/16 (12.5%) | 0/17 (0%) | |||
| Urticaria | 0/3 (0%) | 1/16 (6.3%) | 1/17 (5.9%) | |||
| Alopecia | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Night sweats | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Seborrhoeic dermatitis | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Drug eruption | 1/3 (33.3%) | 0/16 (0%) | 0/17 (0%) | |||
| Erythema | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
| Erythema multiforme | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Vascular disorders | ||||||
| Haematoma | 0/3 (0%) | 1/16 (6.3%) | 0/17 (0%) | |||
| Flushing | 0/3 (0%) | 0/16 (0%) | 1/17 (5.9%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01492088
Other Study ID Numbers:
- C25002
- 2011-001240-29
- U1111-1158-2613
- 133300410A0384
- NL38209.078.11
First Posted:
Dec 14, 2011
Last Update Posted:
Nov 20, 2018
Last Verified:
Nov 1, 2018