A randomized, open-label, multicenter, phase III, study comparing efficacy and tolerability of the intensified variant ‘dose-dense/dose-intense ABVD’ with an interim PET response-adapted ABVD program at first line therapy in advanced-stage classical Hodgkin Lymphoma (HL).
- Conditions
- Advanced stage (IIB-IV) Hodgkin Lymphoma.MedDRA version: 20.0Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2016-002509-21-IT
- Lead Sponsor
- FONDAZIONE ITALIANA LINFOMI ONLUS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 500
- Histologically confirmed classical HL;
- Previously untreated disease;
- Age 18-60 years;
- Ann Arbor stage IIB with extranodal involvement
and/or mediastinal bulk, III and IV (Appendix A);
- At least one target PET-avid bidimensionally assessable lesion;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ¿2 (Appendix B);
- Adequate organ and marrow function as defined below: absolute neutrophil count >1,0 x10^9/L; platelets >75 x10^9/L;
- Total bilirubin <2 mg/dl without a pattern consistent with Gilbert's syndrome;
- Aspartate Transaminase and Alanine Transaminase (AST/ALT) <3 X institutional Upper Limits of Normality (ULN);
- Creatinine within normal institutional limits or creatinine clearance >50 mL/min/1.73 m2 (Appendix C);
- Females of childbearing must have a negative pregnancy test at medical supervision even if had been using effective contraception;
- Life expectancy > 6 months;
- Able to adhere to the study visit schedule and other protocol requirements;
- Sign (or their legally acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study;
- Access to PET-CT scans facilities qualified by FIL;
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 500
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- Nodular Lymphocyte Predominant HL
- Ann Arbor stage IIB without extranodal involvement and/or bulky
- Prior chemotherapy or radiation therapy
- Pregnant or lactating females
- Known hypertension (as defined by the updated Guidelines [76]), cardiac arrhythmia, conduction abnormalities, ischemic cardiopathy, left ventricular hypertrophy or left ventricular ejection fraction (LVEF) =50% at echocardiography.
- Abnormal QTc interval prolonged (>450 msec in males; >470 msec in women)
- Diffusion lung capacity for CO (DLCO) and/or forced expiratory volume in the 1st second (FEV1) tests <50% of predicted not related to impaired respiratory capacity due to airway compression by mediastinal masses or parenchymal lymphoma (see chapter 16)
- Known cerebral or meningeal disease (HL or any other etiology)
- Prior history of malignancies unless the patient has been free of the disease for five years. Exceptions include the following:
o Basal cells carcinoma of the skin
o Squamous cell carcinoma of the skin
o Carcinoma in situ of the cervix
o Carcinoma in situ of the breast
o Prostate cancer with TNM stage T1a or T1b
- Uncontrolled infectious disease
- Human immunodeficiency virus (HIV) positivity or active infectious A, B or C hepatitis. HBsAg-negative patients with anti-HBc positive antibody can be enrolled provided that Hepatitis B Virus (HBV)-DNA are negative and that antiviral treatment with nucleos(t)ide analogs is provided
- Uncompensated diabetes
- Refusal of adequate contraception
- Any medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to demonstrate the superiority of an intensified ABVD variant (ABVD DD-DI, Experimental arm) over an interim PET response-adapted ABVD treatment (Comparator arm) in improving PFS.;Secondary Objective: a)To compare the anti-lymphoma activity of ABVD DD-DI and interim PET response-adapted ABVD according to Lugano 2014 Classification.<br>b)To compare the Overall Survival of ABVD DD-DI vs. interim PET response-adapted ABVD<br>c)To compare the safety of ABVD DD-DI and interim PET response-adapted ABVD<br>d)To compare the effect of ABVD DD-DI and interim PET response-adapted ABVD on Quality of life (QoL)<br>e)To compare ABVD DD-DI vs. interim PET response-adapted ABVD in term of cost-effectiveness. <br>;Primary end point(s): PFS is defined as the interval elapsing from randomization until lymphoma progression or death as a result of any cause.;Timepoint(s) of evaluation of this end point: 3 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Complete remission rate (CR rate); PET/CT response rate after 2 months of chemotherapy ; Event Free Survival (EFS); Disease free survival (DFS); Overall survival (OS); Acute severe toxicity, acute and delayed pulmonary toxicity, acute and delayed cardiac toxicity. Late toxicity and second malignancies; Quality of life (QoL); Cost-effectiveness analyses;Timepoint(s) of evaluation of this end point: After 2 months of chemotherapy, and after 6 months, at the end of treatment; After 2 months of chemotherapy ; 3 years; 3 years; 3 years; 6 months for acute toxicity and 5yrs for late toxicity; 36 months; 36 months