E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Lymphocytic Leukemia |
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E.1.1.1 | Medical condition in easily understood language |
Chronic lymphocytic leukemia (CLL) is a type of cancer affecting the blood and the bone marrow. |
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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 | PT |
E.1.2 | Classification code | 10008958 |
E.1.2 | Term | Chronic lymphocytic leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 objective of this study to evaluate the impact of venetoclax monotherapy on the quality of life of subjects with relapsed or refractory chronic lymphocytic leukemia (CLL). Quality of life will be assessed by
the Global Health Status/Quality of Life (GHS/QoL) subscale of the
European Organization for Research and Treatment of Cancer Quality of
Life Core Questionnaire (EORTC QLQ‑C30). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate impact of venetoclax
monotherapy on quality of life based on the European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire Chronic
Lymphocytic Leukemia Module (EORTC QLQ-CLL16), EuroQoL 5
Dimension 5 Level Questionnaire (EQ-5D-5L), and the remaining
subscales/items from the EORTC QLQ-C30; overall response rate (ORR);
complete remission rate (CR + CRi); duration of overall response (DOR),
time to progression (TTP), duration of progression-free survival (PFS);
overall survival (OS); and CR rate in BCRi treated subjects. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years.
2. Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
3. Subject has relapsed/refractory disease (received at least one prior therapy).
4. Diagnosis of CLL that meets published 2008 Modified International Workshop on CLL National Cancer Institute – Working Group (IWCLL NCI-WG) Guidelines and:
• has an indication for treatment according to the 2008 Modified IWCLL NCI-WG Guidelines
• has clinically measurable disease (lymphocytosis > 5 × 109/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam)
• subjects with or without the 17p deletion or TP53 mutation are eligible
• subjects who have received prior B-cell receptor inhibitor therapy are
also eligible
5. Adequate bone marrow function as follows:
• platelets ≥ 25,000/mm3 without any of the following:
- transfusion support within 14 days of Screening
- evidence of mucosal bleeding
- known history of major bleeding episode within 3 months of Screening
• hemoglobin ≥ 8.0 g/dL
|
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E.4 | Principal exclusion criteria |
1. Subject has developed Richter's transformation or Prolymphocytic leukemia (PLL)
2. Subject has previously received venetoclax.
3. History of active malignancies other than CLL within the past 2 years prior to first dose of venetoclax, with the exception of:
• adequately treated in situ carcinoma of the cervix uteri
• adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
• previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
4. Active and uncontrolled autoimmune cytopenias (within 2 weeks prior to Screening), including autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), despite low dose corticosteroids.
5. Prior allogeneic stem cell transplant. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be assessed by the GHS/QoLL subscale of the EORTC QLQ-C30. The primary endpoint will be the mean change from baseline (within 72 hours prior to the first does of venetoclax) to Week 48. Scores will be calculated based on the scoring manual. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The date the last enrolled subject has completed their Week 48 disease assessment or after all enrolled subjects have discontinued venetoclax, whichever is earlier, will be defined as the data "cutoff" date for the analyses. |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints will include all multi-item scales and single-item scales from the EORTC QLQ-C30, EORTC QLQ-CLL16 and EQ-5D-5L. Scores will be calculated based on the scoring manual for each instrument. The secondary efficacy endpoints will include the Complete Remission Rate (CR+CRi), Overall Response Rate (ORR), Duration of Overall Response (DOR), Time to Progression (TTP), Duration of Progression-Free Survival (PFS) and Overall Survival (OS). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The date the last enrolled subject has completed their Week 48 disease assessment, or after all enrolled subjects have discontinued venetoclax, whichever is earlier, will be defined as the data "cutoff" date for the analyses. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Argentina |
Australia |
Bulgaria |
Colombia |
Hong Kong |
Hungary |
Mexico |
New Zealand |
Poland |
Romania |
Russian Federation |
Taiwan |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
The end-of-study is defined as the date of the last subject's last visit or date of the last follow up contact, whichever is later. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |