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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01492088
• Date of registration: 12/12/2011
• Prospective Registration: Yes
• Primary sponsor: Millennium Pharmaceuticals, Inc.
• Public title: Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory (r/r) Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
• Scientific 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
• Date of first enrolment: April 16, 2012
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01492088
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

France, Germany, Italy, Mexico, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Medical Monitor
• Affiliation: Millennium Pharmaceuticals, Inc.

Key inclusion & exclusion 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



Age minimum: 2 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Relapsed or Refractory Anaplastic Large-cell Lymphoma

Relapsed or Refractory Hodgkin Lymphoma

Intervention(s)

Drug: Brentuximab vedotin

Primary Outcome(s)

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)]

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)]

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]

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)]

Monomethyl Auristatin E (MMAE) Plasma 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]

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)]

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]

Secondary Outcome(s)

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 Survival (OS) (Phase 1 and 2) [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)]

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)]

Duration of Response (DOR) (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 or end of study (Up to 72 months)]

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)]

Monomethyl Auristatin E (MMAE) Plasma 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]

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)]

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]

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 and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)]

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)]

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)]

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 or end of study (Up to 72 months)]

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]

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 and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)]

Secondary ID(s)

NL38209.078.11

133300410A0384

U1111-1158-2613

2011-001240-29

C25002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 15/05/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01492088