aggressive B-cell lymphoma Diffuse large B-cell lymphoma
Conditions
Interventions
Patients will receive brentuximab vedotin in combination with R-DHAP, followed
in responsive patients by high dose chemotherapy and ASCT
Sponsors
HOVON
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: • CD30 positive DLBCL, i.e. more than 1% of DLBCL cells CD30 positive according to the WHO classification 2008:. - CD30 positive DLBCL, including EBV positive DLBCL - CD30 positive primary mediastinal B-cell lymphoma • Primary refractory to or in first relapse after first line therapy with R-CHOP or R-CHOP-like therapy • Age >= 18 years (upper age limit for ASCT at the discretion of the participating center) • Measurable disease: on CT scan at least 1 lesion/node with a long axis of > 1.5 cm and at least one positive lesion on 18F-FDG PET scan • WHO performance status 0-2 • Adequate hepatic function: • Adequate renal function: • Adequate bone marrow function: • Hemoglobin must be >= 8 g/dL (5.0 mmol/L), transfusion is allowed • Eligible for high-dose chemotherapy and ASCT • Resolution of relevant toxicities from first-line therapy • Life expectancy of > 3 months with treatment • Negative pregnancy test at study entry, if applicable • Female patient is either post-menopausal for at least 1 year before screening visit or surgically sterile or if of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, or agrees to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 12 months after the last dose of study drug • Male patients, even if surgically sterilized, (i.e. status post vasectomy) agree to practice effective barrier contraception, or agrees to completely abstain from heterosexual intercourse, during the entire study period and through 12 months after the last dose of study drug • Written informed consent • Patient is capable of giving informed consent
Exclusion criteria
Exclusion criteria: • Peripheral sensory or motor neuropathy grade >= 2 • Known cerebral or meningeal disease (NHL or any other etiology), including signs and symptoms of progressive multifocal leukoencephalopathy (PML) • Symptomatic neurological disease compromising normal activities of daily living or requiring medications • Transformed lymphoma • DLBCL after organ transplantation • Immunodeficiency-associated B-cell lymphoproliferative disease • Use of other investigational agents within at least 5 half-lives of the most recent agent used prior to study entry • Treatment with myelosuppressive chemotherapy or biological therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1 part Primary endpoint • The rate of patients with serious toxicity during cycle 1-2 of the combination BV-R-DHAP Phase 2 part Primary efficacy endpoint • Metabolic CR rate (PET-CT) after the third cycle of BV-R-DHAP salvage therapy Primary feasibility/toxicity endpoints • Rate of grade 3/4 non-hematological toxicity, including neurotoxicity after each cycle of BV-R-DHAP | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1 part Secondary endpoints • (Serious) Adverse Events during combination treatment • Time to hematological recovery after each cycle of BV-R-DHAP • Time to recovery from non-hematological toxicity after each cycle of BV-R-DHAP • Administration of treatment: dose reductions, interval between cycles, discontinuation rate • Rate of successful PBSC collection (>= 2x106 CD34+ cells/kg) after the third cycle of BV-R-DHAP Phase 2 part Secondary efficacy endpoints • Overall response rate (PR + CR) after the third cycle of BV-R-DHAP salvage therapy (based on the results of the FDG-PET/CT scan) • Overall response rate (PR + CR) after ASCT (based on the results of the FDG-PET/CT scan) • Metabolic CR rate (PET-CT) after ASCT • Fraction of patients (CR/PR) eligible for ASCT who actually undergo ASCT • Progression free survival (PFS), Event free survival (EFS), Overall survival (OS Secondary feasibility/toxicity endpoints • (Serious) Adverse Events during the combination treatment • Time to hematological recovery after each cycle of BV + R-DHAP • Administration of treatment: dose reductions, interval between courses, discontinuation rate • Rate of successful PBSC collection (>= 2 x106 CD34+ cells/kg) after the second or third cycle of BV-R-DHAP • Time to hematological recovery after ASCT • (Serious) Adverse Events after ASCT | — |
Countries
Netherlands
Outcome results
None listed