Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma MedDRA version: 19.1 Level: LLT Classification code 10020328 Term: Hodgkin's lymphoma System Organ Class: 100000004864 MedDRA version: 19.1 Level: LLT Classification code 10065864 Term: Anaplastic large-cell lymphoma, primary systemic type System Organ C
Conditions
Interventions
Trade Name: Adcetris®,
Product Name: Adcetris®
Product Code: SGN-35
Pharmaceutical Form: Powder for concentrate for solution for infusion
Sponsors
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 2 to <18 years (5 to <18 years for patients with HL). 2. Have a 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 diagnosed with any relapsed or refractory CD30+ hematological malignancy [eg, primary mediastinal B-cell lymphoma] may be included in phase 1 of the study.) 3. Patients with sALCL must have documented anaplastic lymphoma kinase (ALK) status. 4. Patients with HL must be in their second or later relapse or have failed systemic chemotherapy either as induction therapy for advanced stage disease or salvage therapy, and be ineligible for, refused, or previously received a stem cell transplant. 5. Patients with relapsed or refractory sALCL must be beyond first remission or refractory to front-line chemotherapy. 6. Performance score =60 from Lansky Play Performance Scale if =16 years 7. Female patients who: • Are surgically sterile, OR • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.) 8. Male patients, even if surgically sterilized (ie, status postvasectomy), who: • Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.) 9. Voluntary written consent (and institution-specific assent as appropriate based upon patient comprehension) must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent/assent may be withdrawn by the patient or patient guardian at any time without prejudice to future medical care. 10. Suitable venous access for the study-required procedures. 11. Clinical laboratory values as specified below within 4 days before the first dose of study drug: • Absolute neutrophil count greater than or equal to 1,500/µL. • Platelet count greater than or equal to 75,000/µL. • Serum bilirubin level less than or equal to 1.5 X ULN upper limits of normal (ULN) or less than or equal to 3 X ULN for patients with an indirect hyperbilirubinemia due to Gilbert’s disease. • Serum creatinine less than or equal to 1.5 X ULN. • Alanine aminotransferase (ALT or SGPT) and aspartate aminotransferase (AST or SGOT) less than or equal to 2.5 X ULN. AST and ALT levels may be elevated up to 5 X ULN if their elevation can be reasonably ascribed to the presence of
Exclusion criteria
Exclusion criteria: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Patients meeting any of the following exclusion criteria are not to be enrolled in the study. If a patient is positive for ANY of the exclusion criteria, the patient will not be eligible for the study. 1. Current diagnosis of primary cutaneous ALCL (those with sALCL are eligible). 2. Received an allogeneic stem cell transplant <3 months prior to first dose of study medication, or presence of polymerase chain reaction (PCR)-detectable CMV in any post allogeneic transplant patient. (Prior PCR positivity that was successfully treated is acceptable provided the baseline PCR result is negative prior to first dose of study drug.) 3. Receiving immunosuppressive therapy. 4. Receiving systemic therapy for chronic graft-versus-host disease (topical therapy is allowed). 5. Previous treatment with any anti-CD30 antibody. 6. Therapeutic monoclonal antibody use within the longer of 6 weeks or 5 plasma half lives. 7. Symptomatic cardiac disease including ventricular dysfunction, coronary artery disease, or arrhythmias, if this would, in the opinion of the investigator or project clinician, interfere with assessment of efficacy or safety of the drug. 8. 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.) 9. Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML. 10. History of cirrhosis. 11. Active systemic viral, bacterial, or fungal infection requiring antimicrobial, antiviral therapy or antifungal therapy within 2 weeks prior to first dose of study drug (routine antimicrobial prophylaxis is acceptable). 12. Concurrent therapy with other anti-neoplastic or experimental agents. 13. Systemic corticosteroid therapy <7 days prior to first dose of study medication. 14. Any serious underlying medical condition that, in the opinion of the investigator or project clinician, would impair the patient’s ability to receive or tolerate the planned treatment. 15. Known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation. 16. Received nitrogen mustard agents, melphalan, or BCNU therapy within 6 weeks prior to first study dose. 17. Prior autologous hematopoietic stem cell infusion < 4 weeks prior to first study dose. 18. Grade 2 or greater unresolved toxicity from prior antineoplastic therapy. 19. Received any strong or listed moderate inhibitor of CYP3A4 < 2 weeks prior to first study dose. (Please refer to the Study Manual for an example list of prohibited CYP3A4 inhibitors.) 20. Grade 2 or greater peripheral neuropathy. 21. Female patients who are both lactating and breastfeeding, or have a positive serum or urine pregnancy test during the screening period or a positive serum or urine pregnancy test on Day 1 be
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective in phase 1 are: • To assess the safety profile and determine the pediatric maximum tolerated dose and/or recommended phase 2 dose of brentuximab vedotin • To assess the pharmacokinetics of brentuximab vedotin The primary objectives in phase 2 include is: • To determine the best overall response rate (complete remission, partial remission) with brentuximab vedotin at the recommended phase 2 dose ; Secondary Objective: Phase 1 Secondary Objectives The secondary objectives in phase 1 are: • To determine the immunogenicity of brentuximab vedotin • To determine best overall response rate (complete remission, partial remission) with brentuximab vedotin • To determine the time to progression, time to response, duration of response, and event-free, progression-free, and overall survival with brentuximab vedotin Phase 2 Secondary Objectives The secondary objectives in phase 2 are: • To determine the time to progression, time to response, duration of response, and event-free, progression-free, and overall survival with brentuximab vedotin • To assess the pharmacokinetics and safety profile of brentuximab vedotin • To determine the immunogenicity of brentuximab vedotin Phase 2 Exploratory Objectives The exploratory objective in phase 2 is: • To assess immune reconstitution ; Primary end point(s): Phase 1 Primary Endpoints: • Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values, and vital sign measurements • Plasma concentrations of brentuximab vedotin, total therapeutic antibody, and MMAE Phase 2 Primary Endpoints: The prim | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1 Secondary Endpoints: • Antitherapeutic antibody (ATA) titer and neutralizing ATA titer • Best Overall response rate (CR, PR) as determined by an independent review facility (IRF) using positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), and clinical assessment, according to International Working Group (IWG) revised response criteria • Time to progression • Time to response • Duration of response • Event-free survival • Progression-free survival • Overall survival Phase 2 Secondary Endpoints: • Time to progression • Time to response • Duration of response • Event-free survival • Progression-free survival • Overall survival • Adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements • Plasma concentrations of brentuximab vedotin, total therapeutic antibody, and MMAE • Anti-therapeutic antibody (ATA) titer and neutralizing ATA titer ;Timepoint(s) of evaluation of this end point: Does not have a specific timepoint. | — |
Countries
France, Germany, Italy, Mexico, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactDrug Information Call Centre
Millennium, Drug Information Call Center
Outcome results
None listed