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Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier:
NCT01492088
First received: December 12, 2011
Last updated: March 10, 2017
Last verified: March 2017

December 12, 2011
March 10, 2017
April 2012
October 2016   (Final data collection date for primary outcome measure)
  • Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ 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 ]
    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) [ 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 ]
    Blood samples were collected and tested for conjugated and unconjugated antibodies.
  • Monomethyl Auristatin E (MMAE) Serum Concentrations (Phase 1) [ 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 ]
    Blood samples were collected and tested for MMAE serum concentrations.
  • Overall Response Rate (ORR) (Phase 1 and 2) [ 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) ]
    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.
  • Adverse events, serious adverse events, assessments of clinical and laboratory values, and vital sign measurements (phase 1) [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 12 months ]
  • Plasma concentrations of brentuximab vedotin, total therapeutic antibody, and monomethyl auristatin E (MMAE) (phase 1) [ Time Frame: All (21 day) Cycles: Day 1; Cycle 1: Days 2, 3, 5, 14; Cycle 2: Days 2 (phase 1 only), 3, 5; Cycle 8: Days 2, 3, 5, 14 ]
    Pharmacokinetics of brentuximab vedotin
  • Number of patients with overall response as determined by an IRF using PET, CT and, clinical assessment according to IWG revised response criteria (phase 2) [ Time Frame: PET: At Screening, Cycles 2 and 7. No additional scans needed after Cycle 7 unless clinically indicated. CT: Screening, Cycle 2, 4, 7, 10, 13, 16 and end of treatment and every 12 weeks thereafter for 12 months ]
    Complete response + partial response
Complete list of historical versions of study NCT01492088 on ClinicalTrials.gov Archive Site
  • Number of Participants with Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2) [ Time Frame: Baseline up to EOT (Up to 15 months) ]
    Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-Baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-Baseline confirmed ATA positive responses) and neutralizing ATA (nATA) status.
  • Overall Response Rate (ORR) (Phase 1) [ Time Frame: 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) [ Time Frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 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) [ Time Frame: 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) [ Time Frame: From first documented response until disease progression (Up to 15 months) ]
    DOR is defined as the time in months from the date of first documentation of a CR response to the date of first documentation of tumor progression or PD per IRF assessment according to IWG criteria. 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) [ Time Frame: Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months) ]
  • Progression Free Survival (PFS) (Phase 1 and 2) [ 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) ]
    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. and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
  • Overall Survival (OS) (Phase 1 and 2) [ Time Frame: Every 6 months after EOT, until the sooner of death, study closure, or 2 years after enrollment of the last participant (Up to 48 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ 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 ]
    Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
  • Serum Concentration of Total Antibodies (Conjugated and Unconjugated) [ 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 ]
    Blood samples were collected and tested for conjugated and unconjugated antibodies.
  • Monomethyl Auristatin E (MMAE) Serum Concentrations (Phase 1 and 2) [ 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 ]
    Blood samples were collected and tested for MMAE serum concentrations.
  • Anti-therapeutic antibody (ATA) titer and neutralizing ATA titer (phase 1 & phase 2) [ Time Frame: At screening, predose Day 1 at Cycle 2 and Cycle 4, and at end of treatment; approximately 28 months ]
    Immunogenicity of brentuximab vedotin
  • Number of patients with overall response as determined by an IRF using PET, CT and, clinical assessment according to IWG revised response criteria (phase 1) [ Time Frame: PET: At Screening, Cycles 2 and 7. No additional scans needed after Cycle 7 unless clinically indicated. CT: Screening, Cycle 2, 4, 7, 10, 13, 16 and end of treatment and every 12 weeks therafter for 12 months ]
    Complete response + partial response
  • Time to progression (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to the date of first documented progressive disease, approximately 40 months ]
  • Time to response (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to the date of first documentation of a confirmed complete or partial response, approximately 12 months ]
  • Duration of response (phase 1 & phase 2) [ Time Frame: From the date of first documentation of a confirmed response to the date of progressive disease, approximately 12 months ]
  • Number of patients with event-free survival (phase 1 & phase 2) [ Time Frame: Duration of study (up to 16 cycles) and for 12 months following last dose; approximately 40 months ]
  • Number of patients with progression-free survival (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to the date of first documented progressive disease or death, approximately 40 months ]
  • Number of patients with overall survival (phase 2) [ Time Frame: From the first dose of study treatment to date of death, approximately 40 months ]
  • Adverse events, serious adverse events, assessments of clinical and laboratory values, and vital sign measurements (phase 2) [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 12 months ]
  • Plasma concentrations of brentuximab vedotin, total therapeutic antibody, and monomethyl auristatin E (MMAE) (phase 2) [ Time Frame: All Cycles: Day 1; Cycle 1: Days 2, 3, 5, 14; Cycle 2: Days 2 (phase 1 only), 3, 5; Cycle 8: Days 2, 3, 5, 14 ]
    Pharmacokinetics of brentuximab vedotin
Not Provided
Not Provided
 
Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
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
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.

The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat people who have relapsed or refractory anaplastic large-cell lymphoma (sALCL) or Hodgkin lymphoma (HL). This study will look at the maximum tolerated dose and/or recommended phase 2 dose 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 (up to 7 cycles).

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 20 cycles.

This multicenter trial is being conducted worldwide. The overall time to participate in this study is 4.5 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.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
  • Hodgkin Lymphoma
  • Anaplastic Large-cell Lymphoma
Drug: Brentuximab vedotin
Brentuximab vedotin IV infusion
Other Names:
  • SGN-35
  • ADCETRIS
  • 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 for up to 7 cycles. 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).
    Intervention: Drug: Brentuximab vedotin
  • Experimental: Brentuximab vedotin: Phase 2
    Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle (starting from Cycle 2), until there is evidence of disease progression or unacceptable toxicity (Up to 20 cycles).
    Intervention: Drug: Brentuximab vedotin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
36
March 2018
October 2016   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
2 Years to 18 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States,   France,   Germany,   Italy,   Mexico,   Netherlands,   Spain,   United Kingdom
 
 
NCT01492088
C25002
2011-001240-29 ( EudraCT Number )
U1111-1158-2613 ( Registry Identifier: WHO )
133300410A0384 ( Registry Identifier: RNEC )
NL38209.078.11 ( Registry Identifier: CCMO )
No
Not Provided
Not Provided
Not Provided
Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Takeda
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP