E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of older patients with newly diagnosed classical 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 | 18.1 |
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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives are to show efficacy of B-CAP and brentuximab
vedotin monotherapy |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are to show the safety and feasibility of B-CAP and
brentuximab vedotin |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
B-CAP group:
-Histologically proven classical Hodgkin lymphoma
-First diagnosis, no previous treatment except prephase as outlined
-Age: 60 years or older
-Advanced stages: Stage IIB with large mediastinal mass and/or
extranodal lesions, stage III or IV disease
-ECOG performance status ≤ 2 or ≤ 3 if due to HL
-CIRS-G score of ≤ 6 and ≤ 3 per organ system (except score 4 for eye,
ear, nose and throat)
-Negative HIV test
-Screening laboratory values must meet the following criteria:
Hemoglobin ≥8.0 g/dl, WBC ≥1500/μl; neutrophils ≥1500/μl; platelets
≥75,000/μl (Unless due to HL) Alkaline phosphatase <3 ULN, AST or ALT
<3 ULN, serum total bilirubin ≤1.5 ULN (unless diagnosed with Gilbert's
Syndrome)* INR 2 and an aPTT 2 ULN unless due to anticoagulation
Creatinine clearance > 40 ml/min as estimated by the Cockroft-Gault
formula*
-Life expectancy > 3 months
Brentuximab vedotin single agent group:
-Histologically proven classical Hodgkin lymphoma
-First diagnosis, no previous treatment
-Age: 60 years or older stage IA to IVB
-CIRS-G score of ≥ 7 or 4 in one organ system (except score 4 for eye,
ear, nose and throat)
-Patients not eligible to curative poly-chemotherapy at the investigators
judgment
-Negative HIV test
-Screening laboratory values must meet the following criteria:
Hemoglobin ≥8.0 g/dl, WBC ≥1500/μl; neutrophils ≥1500/μl; platelets
≥75,000/μl (Unless due to HL) Alkaline phosphatase <3 ULN, AST or ALT
<3 ULN, serum total bilirubin ≤1.5 ULN (unless diagnosed with Gilbert's
Syndrome)* INR 2 and an aPTT 2 ULN unless due to anticoagulation
Creatinine clearance > 40 ml/min as estimated by the Cockroft-Gault
formula* |
|
E.4 | Principal exclusion criteria |
B-CAP group:
-Composite lymphoma or nodular lymphocyte- predominant Hodgkin
lymphoma (NLPHL)
-Prior chemotherapy or radiation for HL except prephase as outlined in
the protocol
-Prior chemotherapy containing anthracyclines
-Concurrent disease which precludes protocol treatment, in particular
the following conditions: Chronic obstructive pulmonary disease
(requiring ≥ 2 inpatient treatments due to exacerbation within 1 year);
History of myocardial infarction ≤ 6 months prior to first dose of study
drug; Symptomatic ischemic heart disease, ongoing arrhythmias of
Grade > 2, or any other cardiac condition (e.g. pericardial effusion
restrictive cardiomyopathy) within 6 months prior to first dose of study
drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is
allowed; Heart failure ≥ NYHA II and/or EF <50% (MUGA scan or
echocardiography); Uncontrolled hypertension despite appropriate
medication; Uncontrolled active infection; Chronic active or persisting
(positive PCR) hepatitis B and/or hepatitis C
-Ongoing long-term (i.e. >6 months) ingestion of corticosteroids (e.g.
for chronic polyarthritis) or antineoplastic drugs (e.g. methotrexate)
-Peripheral neuropathy greater than CTC Grade 1
-Patient's lack of accountability, inability to appreciate the nature,
meaning and consequences of the trial and to formulate his/her own
wishes correspondingly
-Non-compliance
-General intolerance of any protocol medication
- Patients who have a relationship of dependence or
employer-employee relationship to the sponsor or the investigator
-Committal to an institution on judicial or official order
-Participation in another interventional trial that could interact with this trial
Brentuximab vedotin single agent group:
-Composite lymphoma or nodular lymphocyte- predominant Hodgkin
lymphoma (NLPHL)
-Prior chemotherapy or radiation for HL except prephase as outlined in
the protocol
-Ongoing long-term (i.e. >6 months) ingestion of corticosteroids (e.g.
for chronic polyarthritis) or antineoplastic drugs (e.g. methotrexate)
-Peripheral neuropathy greater than CTC Grade 1
-Patient's lack of accountability, inability to appreciate the nature,
meaning and consequences of the trial and to formulate his/her own
wishes correspondingly
-Non-compliance
-General intolerance of any protocol medication
-Patients who have a relationship of dependence or employer-employee
relationship to the sponsor or the investigator
-Committal to an institution on judicial or official order
-Participation in another interventional trial that could interact with this
trial |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint of the study is the objective response rate (ORR),
defined as the proportion of patients having CR, CRr or PR in the
centrally reviewed restaging after six cycles of chemotherapy. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints include the complete remission rate assessed after
the end of treatment, progression-free survival (PFS) at three years,
overall survival (OS), OSHL and PFSHL at three years (defined as OS and
PFS but deaths for known reasons other than HL or toxicity of treatment
are censored and not considered as failures), the frequency of adverse
events and the relative dose intensity of the novel brentuximab vedotin -containing
B-CAP regimen or brentuximab vedotin. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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 | Yes |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |