BRENTUXIMAB VEDOTIN for Diffuse large B-cell lymphoma (DLBCL) | Non-Hodgkin lymphoma (NHL)

Inclusion criteria

• {"criterion_text":"- 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\n- Eligible for high-dose chemotherapy and ASCT\n- Resolution of relevant toxicities from first-line therapy\n- Life expectancy of > 3 months with treatment\n- Negative pregnancy test at study entry, if applicable\n- 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\n- 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\n- Written informed consent\n- Patient is capable of giving informed consent\n- Primary refractory to or in first relapse after first line therapy with R-CHOP or R-CHOP-like therapy\n- Age ≥ 18 years (upper age limit for ASCT at the discretion of the participating center)\n- 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\n- WHO performance status 0-2\n- Adequate hepatic function\n- Adequate renal function\n- Adequate bone marrow function\n- Hemoglobin must be ≥ 8 g/dL (5.0 mmol/L), transfusion is allowed"}

Exclusion criteria

• {"criterion_text":"- Peripheral sensory or motor neuropathy grade ≥ 2\n- History of another malignancy less than 3 years before study inclusion, or previously diagnosed with another malignancy and have evidence of residual disease, with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 and carcinoma in situ of the uterine cervix\n- Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin\n- Active hepatitis B or C infection\n- HIV positivity\n- Radiation therapy within 8 weeks prior to start of protocol treatment. Emergency radiation therapy is allowed, as long as measurable disease (at non-irradiated sites) persists\n- Patients with a serious psychiatric disorder that could, in the investigator's opinion, potentially interfere with the completion of treatment according to protocol\n- Major organ dysfunction, unless NHL-related\n- Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study\n- Thyroid abnormalities when thyroid function cannot be maintained in the normal range by medication\n- Current participation in another clinical trial interfering with this trial\n- Known cerebral or meningeal disease (NHL or any other etiology), including signs and symptoms of progressive multifocal leukoencephalopathy (PML)\n- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule\n- Claustrophobia to the extent that PET-CT is impossible\n- Symptomatic neurological disease compromising normal activities of daily living or requiring medications\n- Transformed lymphoma\n- DLBCL after organ transplantation\n- Immunodeficiency-associated B-cell lymphoproliferative disease\n- Use of other investigational agents within at least 5 half-lives of the most recent agent used prior to study entry\n- Treatment with myelosuppressive chemotherapy or biological therapy ≤ 4 weeks before study entry\n- Female patients who are breast feeding"}

Primary endpoints

• {"endpoint_text":"- Phase 1 part: The rate of patients with serious toxicity during cycle 1-2 of the combination BV-R-DHAP. Phase 2 part: 1) Primary efficacy endpoint: Metaftabolic CR rate (PET-diagnostic CT) er the third cycle of BV-R-DHAP salvage therapy. 2) Primary feasibility/toxicity endpoints: Rate of grade 3/4 non-hematological toxicity, including neurotoxicity after each cycle of BV-R-DHAP","definition_or_measurement_approach":"Phase 1: rate of patients with serious toxicity during cycles 1-2 of BV-R-DHAP. Phase 2 efficacy: metabolic complete response (CR) rate assessed by PET-CT after the third cycle of BV-R-DHAP. Phase 2 feasibility/toxicity: rate of CTCAE grade 3/4 non-hematological toxicity, including neurotoxicity, assessed after each cycle."}

Secondary endpoints

• {"endpoint_text":"- Phase 1 part: (Serious) Adverse Events during combination treatment\n- Phase 1 part: Time to hematological recovery after each cycle of BV-R-DHAP\n- Phase 1 part: Time to recovery from non-hematological toxicity after each cycle of BV-R-DHAP\n- Phase 1 part: Administration of treatment: dose reductions, interval between cycles, discontinuation rate\n- Phase 1 part: Rate of successful PBSC collection (≥ 2x106 CD34+ cells/kg) after the third cycle of BV-R-DHAP\n- Phase 2 part: 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)\n- Phase 2 part: Overall response rate (PR + CR) after ASCT (based on the results of the FDG-PET/CT scan)\n- Phase 2 part: Metabolic CR rate (PET-CT) after ASCT\n- Phase 2 part: Fraction of patients (CR/PR) eligible for ASCT who actually undergo ASCT\n- Phase 2 part: Progression free survival (PFS), Event free survival (EFS), Overall survival (OS)\n- Phase 2 part: (Serious) Adverse Events during the combination treatment\n- Phase 2 part: Time to hematological recovery after each cycle of BV + R-DHAP\n- Phase 2 part: Administration of treatment: dose reductions, interval between courses, discontinuation rate\n- Phase 2 part: Rate of successful PBSC collection (≥ 2 x106 CD34+ cells/kg) after the second or third cycle of BV-R-DHAP\n- Phase 2 part: Time to hematological recovery after ASCT\n- Phase 2 part: (Serious) Adverse Events after ASCT","definition_or_measurement_approach":"AE endpoints: (Serious) adverse events collected and graded (CTCAE). Hematological recovery: time to recovery after each cycle or after ASCT (per protocol definitions). PBSC collection success defined as ≥ 2 x10^6 CD34+ cells/kg. Response and metabolic CR endpoints based on FDG-PET/CT assessments. Survival endpoints: PFS, EFS, OS measured from defined baseline per protocol."}

Belgium

Earliest CTIS Part Ii Submission Date

23-01-2024

Latest Decision Or Authorization Date

25-11-2024

Processing Time Days

307

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

23-01-2024

Latest Decision Or Authorization Date

13-11-2024

Processing Time Days

295

Number Of Sites

6

Number Of Participants

5

Netherlands

Earliest CTIS Part Ii Submission Date

23-01-2024

Latest Decision Or Authorization Date

13-11-2024

Processing Time Days

295

Number Of Sites

9

Number Of Participants

30

Primary sponsor

Full Name

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Medication packaging, storage, distribution","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"VUmc Stichting","duties_or_roles":"HOVON Pathology Facility and Biobank (HOP): Pathology review; HOVON Imaging Working group","organisation_type":"Hospital/Clinic/Other health care facility"}