Overview

This trial is active, not recruiting.

Conditions hodgkin lymphoma, anaplastic large-cell lymphoma
Treatment brentuximab vedotin
Phase phase 1/phase 2
Sponsor Millennium Pharmaceuticals, Inc.
Start date April 2012
End date October 2016
Trial size 30 participants
Trial identifier NCT01492088, 133300410A0384, 2011-001240-29, C25002, NL38209.078.11, U1111-1158-2613

Summary

This is a phase 1/2, open-label, single-agent, multi-center, dose-escalation study of brentuximab vedotin in pediatric patients with relapsed or refractory systemic anaplastic large-cell lymphoma or Hodgkin lymphoma

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
brentuximab vedotin
brentuximab vedotin SGN-35
Brentuximab vedotin will be administered by intravenous (IV) infusion once every 21 days. Each 21-day treatment cycle is composed of 1 day study drug treatment, followed by a monitoring period of 20 days. Patients may receive brentuximab vedotin for up to 16 cycles. Treatment with brentuximab vedotin beyond 16 cycles may be allowed for responding patients after discussion between the investigator and medical monitor. Following the final dose of brentuximab vedotin patients will be monitored for safety for a minimum of 30 days. Patients will be followed for progression-free survival (PFS) and overall survival (OS) every 12 weeks for 12 months after the end of treatment (EOT) visit. Thereafter, assessment for OS will continue every 6 months until the sooner of death or study closure or a maximum of 2 years after enrollment of the last patient.

Primary Outcomes

Measure
Number of 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
Overall response rate (CR, PR) as determined by an IRF using PET, CT, MRI 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 scans and MRI: Screening, Cycle 2, 4, 7, 10, 13, 16 and end of treatment and every 12 weeks thereafter for 12 months

Secondary Outcomes

Measure
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
Overall response rate (CR, PR) as determined by an IRF using PET, CT, MRI 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 scans and MRI: Screening, Cycle 2, 4, 7, 10, 13, 16 and end of treatment and every 12 weeks therafter for 12 months
Time to progression (phase 1 & phase 2)
time frame: From the first dose of study treatment to the date of first documented progressive disease
Time to response (phase 1 & phase 2)
time frame: From the first dose of study treatment to the date of first documentation of a complete or partial response
Duration of response (phase 1 & phase 2)
time frame: From the date of first documentation of a response to the date of progressive disease
Event-free survival (phase 1 & phase 2)
time frame: From first dose until treatment failure
Progression-free survival (phase 1 & phase 2)
time frame: From the first dose of study treatment to disease progression or death
Overall survival (phase1 and phase 2)
time frame: From the first dose of study treatment to date of death
Number of 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
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 3, 5; Cycle 8: Days 2, 3, 5, 14

Eligibility Criteria

Male or female participants from 2 years up to 18 years old.

Inclusion Criteria: - Male or female patients aged 2 to <18 years (5 to <18 years for Hodgkin lymphoma (HL)) - Diagnosis of systemic anaplastic large-cell lymphoma, or Hodgkin lymphoma for which standard, curative, life-prolonging, or palliative treatment does not exist or is no longer effective - Patients with systemic anaplastic large-cell lymphoma (sALCL) must have documented anaplastic lymphoma kinase (ALK) status and must be beyond first remission or refractory to front-line chemotherapy - Patients 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 - Patients 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 patients 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 patient - 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 patients 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 - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

Additional Information

Official title A Phase 1/2 Study of Brentuximab Vedotin in Pediatric Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Millennium Pharmaceuticals, Inc..
Location data was received from the National Cancer Institute and was last updated in August 2016.