Relapsed or refractory Hodgkin's lymphoma after first-line chemotherapy or at high risk of failure, as defined by persistence of PET-positivity after the first two courses of first-line chemotherapy in elderly patients = 60 years of age. MedDRA version: 20.0 Level: LLT Classification code 10020328 Term: Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10020234 Term: Hodgkin's
Conditions
Interventions
Product Name: Camidanlumab tesirine
Product Code: [ADCT-301]
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Camidanlumab Tesirine
Current Sponsor code: ADCT-301
Conc
Sponsors
ISTITUTO EUROPEO DI ONCOLOGIA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically proven classical Hodgkin Lymphoma • Biopsy proven cHL in case of relapse or refractory disease after the end of first-line treatment; biopsy will not be required for patients with a positive PET after 2 cycles of front-line treatment • Age greater 60 years • Written informed consent • Eastern Cooperative Oncology Group (ECOG) Performance status =65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: • Patients aged equal or less than 60 years • Patients with nodular lymphocyte-predominant HL • Any prior malignancy at other sites diagnosed or treated within 3 years before the first dose and/or evidence of residual disease, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix and adequately treated basal or squamous cell carcinoma of the skin. • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML. • Symptomatic neurologic disease compromising instrumental activities of daily living or requiring medication. • History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]) (subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition only requiring hormone replacement may be enrolled). • History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis) or other central nervous system autoimmune disease (e.g., poliomyelitis, multiple sclerosis). • Patient who had major surgery less than 20 days before start of treatment • Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose. History of recent infection (within 4 weeks) considered to be caused by one of the following pathogens: SARS-CoV-2, HSV1, HSV2, VZV, EBV, CMV, measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, enterovirus D68. Patient presenting an uncontrolled infectious disease, including patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and currently receiving antiretroviral therapy. Patients with active HBV infection defined by detection of HBs Ag positivity or active Hepatitis C (if antibody [Ab]+ then polymerase chain reaction [PCR]+) indicating acute or chronic infection will be excluded. However patients with viral load defined as negative could be included. Patients with prior history of hepatitis B infection, but immune, with only IgG hepatitis core antibody + (HBcAb+) must receive anti-viral prophylaxis (e.g., lamivudine 100mg po daily) for at least 1 week prior to the first dose of ADCT-301 and throughout all treatment and for at least 12 months after the last ADCT-301 dose. • Patients with uncompensated diabetes mellitus and fasting glucose levels over 180 mg/dl. • Patients with dementia or an altered mental state or past psychiatric conditions that would preclude the understanding and rendering of informed consent and with the ability to comply with the study protocol • Known history of any of the following cardiovascular conditions o Myocardial infarction within 3 months of enrollment o New York Heart Association (NYHA) Class III or IV heart failure o Evidence of current severe uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities, including congenital long QT syndrome, or a corrected QTc interval of = 480 ms, at screening unless secondary to pacemaker or bundle branch block
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ADCT-301 as second-line therapy in elderly classical Hodgkin Lymphoma patients, in terms of complete remission (CR) rate, according to the Lugano Response Criteria (Lugano 2014);Secondary Objective: To better define the efficacy and safety of ADCT-301 in terms of: •Overall Response (OR) •Stable disease (SD) •Progressive disease (PD) •Duration of response •Progression-Free Survival (PFS) at 2 years and median PFS •Overall Survival (OS), at 2 years and median OS •Drop-out rate •Rate of treatment discontinuation due to AE or treatment intolerance •Safety, as measured by incidence of grade 3-4 hematologic and extra-hematological adverse events according to NCI CTCAE version 4.0. •Assessment of comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), loss of activities of daily living (ADLs) before, after cycle 3 and after the end of treatment • Assessment of quality of life using the EQ-5D-5L (EuroQoL Group, 1990) and the FACT-Lym, a lymphoma-specific subscale for the Functional Assessment of Cancer Therapy (FACT);Primary end point(s): Metabolic complete remission rate according to the 2014 Lugano classification as determined by central review in all-treated patients;Timepoint(s) of evaluation of this end point: From baseline (screening), after 3 cycles (PET-3) within 1 week prior to cycle 4, after 4 ¿ 2 weeks from cycle 6 (PET-6); if mCR at PET-6, then after 4 ¿ 2 weeks from cycle 8 (EOT). If no progression at EOT, then CT or MRI will be performed every 12 (± 2) weeks until 1 year from EOT, then every 6 months until disease progression, up to 3 years from EOT. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall Response rate (ORR) defined as the percentage of treated patients with a best overall response of CR or PR; • Duration of response (DOR) defined as the time from the first documentation of tumor response to disease progression or death; • Overall Survival (OS), defined as the time from first dose of study drug until death due to any cause; • Frequency and severity of AEs and SAEs; • Change from Baseline in HRQoL as measured by EuroQoL–5 Dimensions–5 Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym); • Progression-Free Survival (PFS), defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause;Timepoint(s) of evaluation of this end point: From baseline (screening), after 3 cycles (PET-3) within 1 week prior to cycle 4, after 4 ¿ 2 weeks from cycle 6 (PET-6); if mCR at PET-6, then after 4 ¿ 2 weeks from cycle 8 (EOT). If no progression at EOT, then every 12 (± 2) weeks until 1 year from EOT, then every 6 months until disease progression, up to 3 years from EOT.; From baseline (screening), after 3 cycles (PET-3) within 1 week prior to cycle 4, after 4 ¿ 2 weeks from cycle 6 (PET-6); if mCR at PET-6, then after 4 ¿ 2 weeks from cycle 8 (EOT). If no progression at EOT, then every 12 (± 2) weeks until 1 year from EOT, then every 6 months until disease progression, up to 3 years from EOT.; OS: from baseline (screening) until End of study.; AE/SAE: From informed consent signature until EOT or maximum of 30 days after last dose, th | — |
Countries
Italy
Contacts
Public ContactUFFICIO STUDI CLINICI ED ATTIVITA'
ISTITUTO EUROPEO DI ONCOLOGIA
Outcome results
None listed