Hodgkin lymphoma MedDRA version: 20.0 Level: HLGT Classification code 10025319 Term: Lymphomas Hodgkin's disease System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: SGN-35
Product Code: SGN-35
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
INN or Proposed INN: Brentuximab vedotin
CAS Number: 914088-09-8
Other descr
Sponsors
Acedemic Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed CD30+ classical HL (central pathology review; results not required to enroll the patient in the study), primarily refractory to first line chemotherapy or in first relapse after any polychemotherapy regimen (e.g. ABVD, baseline BEACOPP or escalated BEACOPP, or other induction regimens) • In case of relapse, the relapse must be histologically confirmed. In case histology is not possible, at least confirmation of the relapse by FNA is required. • Measurable disease, as defined in Appendix C i.e. CT scans showing at least 2 or more clearly demarcated lesions with a long axis = 1.5 cm and a short axis diameter = 1.0 cm, or 1 clearly demarcated lesion with a long axis = 2.0 cm and a short axis diameter = 1.0 cm. These lesions must be FDG-positive • Age = 18 years (upper age limit for auto-PBSCT at the discretion of the participating center) • WHO = 2 (see appendix A) • Life expectancy of > 3 months with treatment • No major organ dysfunction, unless HL-related • Total bilirubin 60 ml/min as estimated by the Cockroft&Gault formula (appendix D) • Absolute neutrophil count = 1.5x109/L, unless caused by diffuse bone marrow infiltration by the HL • Platelets = 100x109/L, unless caused by diffuse bone marrow infiltration by the HL • Hemoglobin must be >8 g/dL • Written informed consent • Able to adhere to the study visit schedule and other protocol requirements • Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse. • Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse. • Eligible for high dose chemotherapy and autologous peripheral blood stem cell transplantation • Resolution of toxicities from first-line therapy Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 74 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: • Peripheral sensory or motor neuropathy grade = 2 • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML • Symptomatic neurologic disease compromising normal activities of daily living or requiring medications • Patients who have been using other investigational agents within at least 5 half lives of the most recent agent used prior to enrollment in the study • Patients who were treated with myelosuppressive chemotherapy or biological therapy = 4 weeks before study inclusion • Female patients who are both lactating and breast feeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug or adults of reproductive potential who are not using effective birth control methods. • Patients with any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose • Patients who have a history of another primary 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 • Patients with known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin. • Patients with known HIV seropositivity, known hepatitis B surface antigen-positivity, or known or suspected active hepatitis C infection • Patients receiving 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. • Patients with a serious psychiatric disorder that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to the protocol • Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study such as: – unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction = 6 months prior to first study drug, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents = 6 months before study drug start – severely impaired pulmonary function as defined as spirometry and DLCO (diffusing capacity of the lung for carbon monoxide) that is 50% or less of the normal predicted value and/or O2 saturation that is 90% or less at rest on room air – any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study • nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study drug, such as severe hypertension that is not controlled with medical management and thyroid abnormalities when thyroid function cannot be maintained in the normal range by medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I • To identify the feasibility and RDL (recommended dose level) of BV in combination with DHAP, in a 21-day schedule Phase II • To demonstrate the efficacy and safety of BV in combination with DHAP as salvage treatment (establish the fraction of responding patients – metabolic CR – as judged by PET-CT after the third cycle, and establish the rate of grade ¾ non-hematological toxicity, including neurotoxicity). ;Secondary Objective: Phase I • To assess the toxicity of BV in combination with DHAP • To assess the success rate of autologous peripheral blood stem cell harvest after 2 courses of BV-DHAP Phase II • To assess the ORR (CR and PR) after 3 cycles of BV-DHAP and after auto-PBSCT • To assess the toxicity profile of BV in combination with DHAP • To assess hematological recovery after each cycle of BV-DHAP • To assess the feasibility of harvesting an autologous peripheral blood stem cell graft after 2 cycles of BV-DHAP • To assess the fraction of patients (CR/PR) eligible for auto-PBSCT who actually undergo auto-PBSCT • To assess peripheral blood neutrophil and platelet recovery after auto-SCT • To evaluate PFS, EFS and OS with this treatment regimen • To identify predictive factors for response, PFS, EFS and OS (exploratory analysis);Primary end point(s): ? The rate of patients with severe toxicity (defined as DLT’s, see paragraph 7.2) during cycle I-III of the combination treatment (BV + DHAP) ? RDL of BV-DHAP for the phase II part of the study ? Metabolic CR rate (PET-CT) after the third cycle of BV-DHAP reinduction therapy;Timepoint(s) of evaluation of this end point: • At entry • Prior to each cycle of BV-DHAP • After the second cycle of BV-DHAP • After the 3rd cycle of BV-DHAP • 6 weeks after ASCT • End of protocol treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? (Severe) Adverse Events during the combination treatment ? Time to hematological recovery after each cycle of BV + DHAP ? Time to recovery from non-hematological toxicity after each cycle of BV + DHAP. ? Administration of treatment: dose reductions, interval between cycles, discontinuation rate ? Rate of successful PBSC collection (= 2x106 CD34+ cells/kg) after the second cycle of BV- DHAP ? Overall response rate (PR + CR) after the third cycle of BV-DHAP reinduction therapy (based on the results of the FDG-PET/CT scan) ? Overall response rate (PR + CR) after auto-PBSCT (based on the results of the FDG-PET/CT scan) ? Metabolic CR rate (PET-CT) after auto-PBSCT ? Fraction of patients (CR/PR) eligible for auto-PBSCT who actually undergo auto-PBSCT ? Progression free survival (PFS) and event free survival (EFS) ? Overall survival (OS) ;Timepoint(s) of evaluation of this end point: • At entry • Prior to each cycle of BV-DHAP • After the second cycle of BV-DHAP • After the 3rd cycle of BV-DHAP • 6 weeks after ASCT • End of protocol treatment • During follow up every 3 months for 2 years and every 6 months thereafter until 5 years after last treatment | — |
Countries
Denmark, France, Netherlands
Contacts
Public ContactEdith van Dijkman
Academic Medical Center
Outcome results
None listed