Patients with Relapsed /Refractory Classical Hodgkin's Lymphoma MedDRA version: 20.1 Level: LLT Classification code 10080208 Term: Classical Hodgkin lymphoma System Organ Class: 100000004864
Conditions
Sponsors
Fundación GELTAMO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with classical HL CD30+ confirmed histologically (either at the time of diagnosis / at the time of first relapse) will be included in the trial. A biopsy at the time of relapse / demonstration of primary refractoriness is highly recommended. Patients diagnosed with 1st relapsed/refractory HL (treatment escalation or de-escalation, performed according to interim PET-CT result in first-line therapy, will still be considered as a single prior line, i.e., RATHL or LYSARC trials) will also be considered candidates for the trial. Each patient must meet all of the following inclusion criteria to be enrolled in the study: 1.Male or female patients 18 years or older up to 65 years of age 2.Voluntary written informed consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care 3.Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 highly 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 agrees to completely abstain from heterosexual intercourse 4.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 5.ECOG performance status 0 to 2 6.Measurable disease at time of enrolment (lymphadenopathy/ extranodal mass of at least 1.5 cm) 7.No evidence of neuropathy grade =2 8.Clinical laboratory values as specified below within 7 days before the first dose of study drug: • Absolute neutrophil count = 1,500/µL unless there is known hematologic/solid tumor marrow involvement • Platelet count = 75,000/ µL unless there is known marrow involvement of the disease • Total bilirubin must be 40 mL/minute • Hemoglobin must be = 8g/dL 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 150 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Lymphocyte predominant nodular Hodgkin’s lymphoma 2.Prior treatment with brentuximab vedotin 3.Female patient who is 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 4.Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to the protocol. 5.Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML) Symptomatic neurologic disease compromising normal activities of daily living or requiring medic 6.Any sensory or motor peripheral neuropathy greater than or equal to Grade 2 7.Known history of any of the following cardiovascular conditions • Myocardial infarction within 2 years of enrollment • New York Heart Association (NYHA) Class III or IV heart failure (see Appendix #9)65 • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities • Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50% 8.Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose 9.Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives (or 28 days if the half-lives are unknown) of last dose of that prior treatment 10.Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin. 11.Known human immunodeficiency virus (HIV) positive 12.Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection 13.Focal radiation therapy within 30 days prior to study recruitment 14.Major surgery within 28 days prior to randomization 15.Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluating Efficacy of Salvage Therapy with Brentuximab Vedotin-ESHAP vs ESHAP in Patients with Relapsed / Refractory Classical Hodgkin’s Lymphoma in terms of primary efficacy endpoints.;Secondary Objective: 1.To assess 2-year progression free survival (PFS) and 2-year overall survival (OS) in patients attaining a mCR and treated with BV consolidation 2.To evaluate duration of response and time to progression in patients treated with BV consolidation after attaining a mCR 3.To assess differences in toxicities between ESHAP-BV vs ESHAP 4.To quantify stem cell collection yield 5.To assess impact of second line therapy on 2-year PFS 6.To compare the outcome of patients that attained less than mCR assessing their ORR and CR rates after autoHCT, time to next therapy (TTNT) and OS 7.To assess TTNT2 8.To evaluate the prognostic impact of a negative baseline PET-CT on PFS and OS 9.To evaluate the prognostic impact of metabolic tumor volume in PFS and OS 10.To determine short-term and mid-term toxicity 11.To assess quality of life of patients 12.To predict the risk to develop peripheral neuropathy 13.To explore the concordance between PEC-TC local and central evaluation;Primary end point(s): Treatment response based on Deauville scores 1, 2 (Complete metabolic response) at interim PET-CT;Timepoint(s) of evaluation of this end point: After the 3 first cycles of BV-ESHAP or ESHAP | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: 1- Progression Free Survival (PFS): time from entry onto the study until lymphoma progression or death as a result of any cause 2- Overall Survival (OS): time from entry onto the clinical trial until death as a result of any cause. 3- Duration of response (DOR): time from first documentation of CR or PR to disease progression or death from any cause, whichever occurs first 4- Time to Progression (TTP): time from study entry until lymphoma progression or death as a result of lymphoma. 5- Time to Next Treatment (TTNT): time from the end of primary treatment until the onset of the next therapy. 6- Time to Next Treatment 2 (TTNT2): time from study enrollment to initiation of second line of therapy due to disease progression. 7- Overall response rate, complete response rate 8- Prognostic impact of metabolic tumor volume Patient reported outcomes: 9- Quality of life of patients Secondary safety endpoints: 10- Toxicity 11- Peripheral neuropathy 12- Stem cell collection yield;Timepoint(s) of evaluation of this end point: Secondary efficacy timepoints: 1- Progression Free Survival: 2 years 2- Overall Survival: 2 years 3- Duration of response: throughout the study period 4- Time to progression: throughout the study period 5- Time to next treatment (TTNT): throughout the study period 6- Time to next treatment 2 (TTNT2): throughout the study period 7- Overall response rate, complete response rate: After the 3 first cycles of BV-ESHAP or ESHAP 8- Prognostic impact of metabolic tumor volume: throughout the study period Patient reported outcomes: 9- Quality of life: throughout the study period Secondary safety timepoints: 10- Toxicity: throughout the study period 11- Peripheral neuropathy: throughout the study period 12- Stem cell collection yield: throughout the first 3 cycles of treatment | — |
Countries
Austria, Belgium, Czech Republic, Greece, Israel, Spain
Contacts
Public ContactUnidad de ensayos
Grupo Español de linfomas y trasplante autologo de medula osea (GELTAMO)
Outcome results
None listed