Older Patients with Untreated Hodgkin Lymphoma MedDRA version: 20.1 Level: LLT Classification code 10080208 Term: Classical Hodgkin lymphoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Adcetris
Product Name: brentuximab vedotin
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: BRENTUXIMAB VEDOTIN
CAS Number: 914088-09-8
Other desc
Sponsors
GELTAMO (Grupo Español de Linfomas y trasplante autólogo de médula osea)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Males or females of 60 years of age or older. 2.Previously untreated classical Hodgkin lymphoma (i.e., nodular sclerosis, mixed cellularity, lymphocyte depleted, lymphocyte-rich, and not otherwise specified [NOS]). 3.Stage IIB, III, and IV disease by Ann Arbor classification. 4.Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 5.Patients must have bi-dimensional measurable disease documented in the lymphoma baseline tumor assessment form within 30 days prior to registration (at least 1.5 cm); patients with non-measurable disease in addition to measurable disease must have been assessed within 60 days prior to registration. 6.Patients must have a bone marrow biopsy within 60 days prior to registration. 7.Patients must have a multi gated acquisition scan (MUGA) or echocardiogram within 60 days prior to study registration and the ejection fraction must be >= 50%. 8.Adequate hematologic function, defined as Absolute neutrophil count (ANC) = 1,500/mm3 / 1x109/L and Platelet count =75,000/mm3 / 75x109/L unless there is know marrow involvement of the disease 9.Serum Creatinine 40 mL/minute. 10.Total Bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: 1.Nodular lymphocyte predominant Hodgkin lymphoma 2.Previous treatment with BV or any other prior anti-CD30-based antibody therapy 3. Female patient who is both lactating and breast-feeding or has a positive pregnancy test during the screening period or a positive pregnancy test on Day 1 before the first dose of study drug 4.History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: early stage [stage I or II] breast cancer treated with surgery and radiation +/- hormones [without adjuvant chemotherapy], non-melanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou test [PAP smear]) 5.Known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of PML 6.Any active systemic viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 1 week prior to first dose 7.Known or suspected hepatitis B infection, or known or suspected active hepatitis C infection Known human immunodeficiency virus (HIV) positive 8.Patients with a known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin 9.Patients with dementia or an altered mental state that would preclude the understanding and rendering of informed consent 10.Symptomatic neurologic disease compromising normal activities of daily living or requiring medications 11.Any sensory or motor peripheral neuropathy greater than or equal to 2 12.Known history of any of the following cardiovascular conditions; a. Myocardial infarction within 2 years of enrollment b. New York Heart Association (NYHA) Class III or IV heart failure c. Evidence of uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ib •To identify the maximum tolerated dose (MTD) of Brentuximab Vedotin (BV) in combination with EPEM, by assessment of dose limiting toxicity (DLT) in a 28-day schedule. •To assess the toxicity of the combination of BV with EPEM. Phase II •To assess the efficacy of BV in combination with EPEM by assessment of complete response rate among older patients with HL at the end of scheduled treatment;Secondary Objective: •To evaluate (PFS), (EFS) and (OS) with this treatment regimen •To evaluate the duration of response with this treatment regimen •To evaluate the (ORR) based on best response (Complete Response [CR] and Partial Response [PR]) and the tumor local control rate (CR, PR, and stable disease [SD]) with this treatment regimen. •To assess the safety and tolerability of BV in combination with EPEM: type, frequency, and severity for adverse events (AEs) and relationship of AEs to this treatment regimen. •To assess the effects of therapy on the quality of life, the ability to perform everyday tasks and to determine how often side effects occur. •To evaluate the differential expression of CD30 between patients who achieved a sustained clinical response, and those who have will demonstrate refractory to therapy. •Proposal of Biomarkers for BV: by comparing protein expression and mutational patterns between responders and non-responders to therapy; targets will include:;Primary end point(s): Phase 1 •Dose-limiting toxicity (DLT) of the combination treatment (BV + EPEM) •Maximum tolerated dose (MTD)of BV-EPEM for the phase II part of the study •(Severe) Adverse Events during the combination treatment Phase 2: Complete response (CR) rate after the 6 cycles of BV-EPEM therapy (based on the results of the PET scan).;Timepoint(s) of evaluation of this end point: Phase 1 part: The patients will be monitored closely for adverse events. The number of patients with unacceptable toxicities, requests to stop treatment or death will be determined at day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Progression free survival (PFS): defined as the time from the date of registration to the date of first documented tumor progression or death from any cause, whichever occurs first. •Event free survival (EFS): defined as the time from the date of registration until failure of treatment (either no CR or PR on treatment or relapse) or death as a result of any case. •Overall survival (OS): defined as the time from study entry to death from any cause. All deaths will be included, whether they occur on study or following treatment discontinuation. For patients who have not died, overall survival will be censored at the date of last contact. •Duration of response: defined as the time from first documentation of CR or PR to disease progression or death from any cause, whichever occurs first. • Overall response rate based on best response (CR and PR) and the tumor local control rate (CR, PR, and stable disease [SD]). • Safety and tolerability as assessed by type, frequency, and severity for AEs and relationship of AEs to the combination of BV and EPEM chemotherapy.;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated when the relevant data for all patients are available in the phase 1 and phase 2 | — |
Countries
Spain
Contacts
Public ContactSecretaria Cientifica de GELTAMO
GELTAMO (Grupo Español de Linfomas y trasplante autólogo de médula osea)
Outcome results
None listed