| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| relapsed or refractory Hodgkin Lymphoma |
| rezidiviertes oder refraktäres Hodgkin Lymphom |
|
| E.1.1.1 | Medical condition in easily understood language |
| reappearance of Hodgkin Lymphoma or Hodgkin Lymphoma that did not respond to therapy |
| Rückfall eines Hodgkin Lymphoms oder Hodgkin Lymphom, das auf Therapie nicht ansprach |
|
| 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 | 20.0 |
| 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.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
PHASE I:
Primary:
• To identify the RPTD (recommended phase II dose) of RAD001 in combination with DHAP (Ever-DHAP)
PHASE II:
Primary:
• To demonstrate the efficacy of Ever-DHAP as induction therapy
|
|
| E.2.2 | Secondary objectives of the trial |
PHASE I:
Secondary:
• To assess toxicity and efficacy of Ever-DHAP
PHASE II:
Secondary:
• To compare efficacy and feasibility of Ever-DHAP and Placebo-DHAP
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Histologically confirmed early or late first relapsed classical HL (CR or CRu ˃ 3 months following the end of any polychemotherapy regimen +/- radiotherapy); patients with refractory HL (CR or CRu ≤ 3 months following the end of first line treatment); patients with multiple relapse (any salvage therapy, no prior HDCT or SCT); pathology report based on original tumor tissue/lymph node is acceptable for meeting inclusion criteria, but tumor tissue (slides/block) must be available to be sent for central pathology to confirm diagnosis.
• Age at entry: 18-60 years.
• WHO activity index ≤ 2
• Life expectancy of > 3 months with treatment.
• Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L, platelets ≥ 100 x 109/L, except for HL-related reduced values (e.g. in case of splenomegaly)
• Total bilirubin ≤ 2 x ULN (if >2 x ULN direct bilirubin is required and should be ≤1.5 x ULN)
• Serum creatinine ≤ 2 x ULN
• Normal organ function (except HL-related)
• Patient has given his/her written informed consent to participate in the trial
• Patient agrees to his personal data and tissue material, with due regard for data protection, being used for the study.
• Women of childbearing potential must have had a negative serum pregnancy test.
• Patients capable of swallowing intact study medication tablets and following directions regarding taking study drug, or have a daily caregiver who will be responsible for administering study drug.
|
|
| E.4 | Principal exclusion criteria |
• Liver disease as indicated by ASAT ≥ 3 x ULN (≥ 5 x ULN if liver involvement is present)
• Patients who have a history of another primary malignancy ≤ 3 years, with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 and carcinoma in situ of uterine cervix.
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Oral contraceptives are not acceptable.
• Patients unwilling to or unable to comply with the protocol.
• Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study drug start.
• Patients who had myelosuppressive chemotherapy or biologic therapy < 2 weeks to study inclusion.
• Patients who have previously received systemic mTOR inhibitor (sirolimus, temsirolimus, everolimus, etc).
• Patients with evidence of current central nervous system (CNS) involvement.
• Patients receiving chronic systemic immunosuppressive agents. Inhaled and topical steroids are acceptable. Patients may be receiving stable (not increased within the last month) chronic doses of corticosteroids with a maximum dose of 20 mg of prednisone or 10 mg of dexamethasone per day, if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency or asthma.
• Patients with active, bleeding diathesis.
• Patients with known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to any protocol medication.
• Patients receiving ongoing radiation therapy
• Patients with a psychiatric, addictive or any disorder which compromises their ability to give truly informed consent for participation in this study.
• Non-compliance: Refusal of blood products during treatment, epilepsy, drug dependency, change of residence to abroad, prior cerebral injury or similar circumstances that appear to make protocol treatment or long-term follow-up impossible
• Antiepileptic treatment
• poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN
• Patients with a known history of HIV seropositivity, chronic active hepatitis
• Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
– unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first study drug, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents ≤ 6 months before study drug start
– severely impaired lung function as defined by spirometry (FEV1) and DLCO (diffusing capacity of the lung for carbon monoxide) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
– any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
– nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study drug, such as severe hypertension that is not controlled with medical management and thyroid abnormalities whose thyroid function cannot be maintained in the normal range by medication |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
PHASE I:
Primary:
• The rate of patients experiencing DLTs during 2 cycles of the combination therapy
PHASE II:
Primary efficacy endpoint:
• CR rate after induction therapy (CT-based only)
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I:
During therapy
Phase II:
After 2 cycles of therapy |
|
| E.5.2 | Secondary end point(s) |
PHASE I:
Secondary:
• Adverse events during combination therapy
• Tumor related results of therapy or death
• Treatment administration (dose reductions of chemotherapy, duration of treatment)
• Time to recovery after end of treatment
• Stem cell mobilization
PHASE II:
Secondary efficacy endpoints:
• CT-based tumor status after induction therapy
• PET/CT-based tumor status after induction therapy
• Progression free survival (PFS)
• Overall Survival (OS)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase I:
During and directly after therapy
Phase II:
Restaging after therapy and follow-up of two years |
|
| 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) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| 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
| 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 | 25 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 0 |
| 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
|
| Follow-Up of two years after the last patient has finished final restaging to assess progression free and overall survival |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
Print
