| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced stage Hodgkin Lymphoma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10080208 |
| E.1.2 | Term | Classical Hodgkin lymphoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020206 |
| E.1.2 | Term | Hodgkin's disease |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10020243 |
| E.1.2 | Term | Hodgkin's disease NEC |
| E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | HLGT |
| E.1.2 | Classification code | 10025319 |
| E.1.2 | Term | Lymphomas Hodgkin's disease |
| E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10005329 |
| E.1.2 | Term | Blood and lymphatic system disorders |
| E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10029104 |
| E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The main objective of this trial is to assess whether treatment adaptation based on a very early FDG-PET/CT results in improved efficacy while minimizing treatment toxicity in advanced stage HL patients treated with BV-containing regimens, BrAVD and BrECADD.
This will be primarily assessed by modified progression-free survival.
|
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
• To assess the rate of FDG-PET negativity (Deauville score 1-3) after 1 cycle of BrAVD
• To assess response according to Lugano Criteria at end of protocol treatment i.e. after chemotherapy and after radiotherapy (if administered), as defined by FDG-PET/CT
• To assess the safety and tolerability of the different BV containing regimens
• To assess the safety and tolerability of radiotherapy in the context of BrAVD and BrECADD
• To assess efficacy in terms of PFS and OS
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Previously untreated, histologically proven classical Hodgkin lymphoma;
• Staged by PET with diagnostic-quality CT (i.v. contrast).
- Clinical stages according to Lugano 2014 and based on FDG/PET CT:Stage IIB with large mediastinal mass > 1/3 max transverse diameter thorax and/or extranodal lesion(s) (GHSG)
- Stage III - IV
• Participation in translational research is mandatory and therefore patient must consent to additional blood samples at multiple time points in the study. In addition, sufficient tissue must be available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block).
• Age ≥18 and ≤60
• WHO performance status 0-2
• Patient demonstrates adequate organ function as defined in the protocol.
• Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
• Patients of childbearing / reproductive potential should use two birth control methods, as defined by the investigator, from the time of signing the informed consent form , and throughout the entire study and for 6 months after the last dose of treatment.
• Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
• Absence of any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations. |
|
| E.4 | Principal exclusion criteria |
• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencenphalopathy
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
• Sensory or motor peripheral neuropathy greater than or equal to grade 2 according to CTCAE version 5.0
• Any of the following cardiovascular conditions or values:
- within 6 months before registration:
• A left-ventricular ejection fraction <50%
• New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D).
• 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
• symptomatic coronary heart disease (stable angina pectoris is allowed)
• severe uncontrolled hypertension defined as blood pressure (BP) >150/100 mmHg despite optimal antihypertensive treatment
- within 2 years before registration:
• Myocardial infarction
• Patients with poorly controlled diabetes mellitus (HbA1c > 7.5 % or a fasting blood sugar > 200 mg/dL).
• Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to registration.
• Known HIV infection, chronic active hepatitis C, HBV positivity (HBsAg + patients; HBsAg -/HBcAb+/HBV DNA+ patients).
Note: HBsAg-/HBV DNA – patients are eligible; patients who are seropositive due to vaccination are eligible
• Concomitant or previous malignancies within the past 5 years with the exception of adequately treated carcinoma in situ of the cervix , nonmelanoma skin cancer.
• Previous treatment with anti CD30 antibodies
• Known hypersensitivity to any excipient contained in Brentuximab Vedotin formulation and other study drugs. Refer to Summary Product Characteristics for list of excipients.
• Concurrent anti-cancer treatment or use of any investigational agent(s) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Modified progression-free survival rate at 2 years after start of treatment (2yr-mPFS for each party).
The following are considered events for the primary endpoint: progression/relapse; start of new treatment for cHL when not in CR after completing protocol treatment; death from any cause.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Modified progression-free survival rate at 2 years (2yr-mPFS). Modified PFS is defined as the time interval between the treatment start date and the date of the first of:
• Progressive disease (PD)
• Start of new treatment for cHL when not in CR at the end of protocol treatment; in this case, the date of mPFS is the date of the FDG-PET/CT scan at the end of protocol treatment. Switching therapy prior to end of protocol treatment for reasons other than PD is not considered an event for mPFS. "End of protocol treatment" refers to completion of the planned protocol treatment with no more than 1 missed cycle, including radiotherapy on PET positive lesions if administered
• Death due to any cause
Patients without any of these events will be censored at the last response assessment date. |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints are:
• FDG-PET result (positive/negative) after 1 cycle of BrAVD (central assessment)
• Response rate according to Lugano Criteria at end of protocol treatment i.e. after chemotherapy and after radiotherapy (if administered), as defined by FDG-PET/CT
• Progression-free survival (where progression, relapse and death from any cause are considered events).
• Overall survival
• Safety and tolerability
• Response according to RECIL 2017
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 5 Years after end of treatment |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Treatment strategy based on FDG-PET results |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 23 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Egypt |
| Belgium |
| Croatia |
| Denmark |
| France |
| Netherlands |
| Poland |
| Portugal |
| Slovakia |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of study occurs when all of the following criteria have been
satisfied:
• All patients have completed their end of study visit. If a participant
discontinues the follow-up for one of the following reasons: withdrawal of consent, loss to follow-up, or death, the end of study participation is defined as the time point when one of these events occurred.
• The trial is mature for all analyses defined in the protocol and the
database has been cleaned and frozen for these analyses.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 30 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 13 |
Print
