Back to resultsStudy of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory (r/r) Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
Primary Purpose
Relapsed or Refractory Hodgkin Lymphoma, Relapsed or Refractory Anaplastic Large-cell Lymphoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Brentuximab vedotin
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed or Refractory Hodgkin Lymphoma focused on measuring Pediatric, Lymphoma, Hodgkin, Anaplastic Large-cell, Relapsed, Refractory, Drug therapy
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Brentuximab vedotin: Phase 1
Brentuximab vedotin: Phase 2
Arm 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. 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).
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.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1)
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)
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)
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)
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)
Blood samples were collected and tested for conjugated and unconjugated antibodies.
Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1)
Blood samples were collected and tested for MMAE plasma concentrations.
Overall Response Rate (ORR) (Phase 1 and 2)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
Blood samples were collected and tested for conjugated and unconjugated antibodies.
Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1 and 2)
Blood samples were collected and tested for MMAE plasma concentrations.
Full Information
NCT ID
NCT01492088
First Posted
December 12, 2011
Last Updated
November 12, 2018
Sponsor
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01492088
Brief Title
Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory (r/r) Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
April 16, 2012 (Actual)
Primary Completion Date
October 12, 2016 (Actual)
Study Completion Date
April 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Hodgkin Lymphoma, Relapsed or Refractory Anaplastic Large-cell Lymphoma
Keywords
Pediatric, Lymphoma, Hodgkin, Anaplastic Large-cell, Relapsed, Refractory, Drug therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Brentuximab vedotin: Phase 1
Arm Type
Experimental
Arm 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. 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).
Arm Title
Brentuximab vedotin: Phase 2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Brentuximab vedotin
Other Intervention Name(s)
SGN-35, ADCETRIS
Intervention Description
Brentuximab vedotin IV infusion
Primary Outcome Measure Information:
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)
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)
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)
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
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
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
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)
Secondary Outcome Measure Information:
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
City
Aurora
State/Province
Colorado
Country
United States
City
Kansas City
State/Province
Missouri
Country
United States
City
New York
State/Province
New York
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Bordeaux Cedex
Country
France
City
Lyon
Country
France
City
Paris Cedex 12
Country
France
City
Berlin
Country
Germany
City
Frankfurt
Country
Germany
City
Giessen
Country
Germany
City
Halle
Country
Germany
City
Munster
Country
Germany
City
Padova
Country
Italy
City
Roma
Country
Italy
City
Mexico Df
Country
Mexico
City
Rotterdam
Country
Netherlands
City
Barcelona
Country
Spain
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Citations:
PubMed Identifier
17242396
Citation
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
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PubMed Identifier
32596842
Citation
Suri A, Mould DR, Song G, Kinley J, Venkatakrishnan K. Population Pharmacokinetics of Brentuximab Vedotin in Adult and Pediatric Patients With Relapsed/Refractory Hematologic Malignancies: Model-Informed Hypothesis Generation for Pediatric Dosing Regimens. J Clin Pharmacol. 2020 Dec;60(12):1585-1597. doi: 10.1002/jcph.1682. Epub 2020 Jun 28.
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PubMed Identifier
30290902
Citation
Locatelli F, Mauz-Koerholz C, Neville K, Llort A, Beishuizen A, Daw S, Pillon M, Aladjidi N, Klingebiel T, Landman-Parker J, Medina-Sanson A, August K, Sachs J, Hoffman K, Kinley J, Song S, Song G, Zhang S, Suri A, Gore L. Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study. Lancet Haematol. 2018 Oct;5(10):e450-e461. doi: 10.1016/S2352-3026(18)30153-4.
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Learn more about this trial
Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory (r/r) Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
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