| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Lymphocytic Leukemia with 17p deletion |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic Lymphocytic Leukemia with 17p deletion |
|
| 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 | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068919 |
| E.1.2 | Term | B-cell chronic lymphocytic leukemia |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
| - To evaluate the overall response rate (ORR) following treatment with idelalisib (IDELA) plus rituximab in subjects with previously untreated chronic lymphocytic leukemia (CLL) with 17p deletion. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of the combination of IDELA and rituximab on the onset, magnitude, and duration of disease control, including duration of response (DOR), progression free survival (PFS), and overall survival (OS)
- To evaluate the effect of the combination of IDELA and rituximab on minimal residual disease (MRD)
- To describe the safety profile observed with the combination of IDELA and rituximab
- To characterize exposure to study treatment with IDELA and rituximab as determined by treatment administration and evaluation of IDELA plasma concentrations over time |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Male or female ≥18 years of age.
2) Documented diagnosis of B-cell CLL, according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008.
3) Presence of 17p deletion in CLL cells as demonstrated by FISH testing performed at a central laboratory.
4) No prior therapy for CLL other than corticosteroids for disease complications.
5) CLL that warrants treatment based on pre-defined criteria.
6) Presence of measurable lymphadenopathy confirmed by the Independent Review Committee (IRC) (defined as the presence of ≥1 nodal lesion that measures ≥2.0 cm in the longest dimension [LD] and ≥1.0 cm in the longest perpendicular dimension [LPD] as assessed by computed tomography [CT] or magnetic resonance imaging [MRI]).
7) ECOG performance status of ≤2.
8) Required baseline laboratory data (within 28 days prior to enrollment) as shown in the protocol.
9) For female subjects of childbearing potential, willing to use a protocol-recommended method of contraception from the signing of informed consent throughout the study treatment period and 30 days from the last dose of IDELA or 12 months from the last dose of rituximab, whichever is later.
10) Male subjects of reproductive potential having intercourse with females of childbearing potential, must agree to utilize protocol specified methods of contraception and refrain from sperm donation from the enrollment visit throughout the study treatment period and up to 3 months from the last dose of IDELA or 12 months from the last dose of rituximab, whichever is later.
11) Lactating females must agree to discontinue nursing before study drug administration.
12) Willing and able to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions.
13) Evidence of a signed informed consent. |
|
| E.4 | Principal exclusion criteria |
1) Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation).
2) Known presence of myelodysplastic syndrome.
3) History of a non-CLL malignancy with the following exceptions:
a) the malignancy has been in remission without treatment for ≥5 years prior to enrollment, or
b) carcinoma in situ of the cervix, or
c) adequately treated basal or squamous cell skin cancer or other localized non-melanoma skin cancer, or
d) asymptomatic prostate cancer without known metastatic disease and with no current requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥1 year prior to enrollment, or
e) DCIS of the breast treated with lumpectomy alone, or
f) Other adequately treated Stage 1 or 2 cancer currently in complete remission.
4) Known hypersensitivity or intolerance to any of the active substances or excipients in the formulations for IDELA, or rituximab.
5) Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment.
6) Ongoing drug-induced liver injury, alcoholic liver disease, non alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
7) History of non-infectious pneumonitis.
8) Ongoing inflammatory bowel disease.
9) History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
10) Ongoing immunosuppressive therapy other than corticosteroids.
11) Received last dose of study drug on another therapeutic clinical trial within 30 days prior to enrollment.
12) Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results.
13) Subject has undergone major surgery other than diagnosis surgery within 30 days prior to enrollment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is Overall response rate (ORR) – defined as the proportion of subjects who achieve a confirmed CR or confirmed partial response (PR) by IRC. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Primary analysis will be performed when all enrolled subjects have completed efficacy, safety, and other assessments through ≥36 weeks of evaluation. The final analysis will be performed at the conclusion of the study. |
|
| E.5.2 | Secondary end point(s) |
• Duration of Response (DOR) – defined as the interval from the first documentation of confirmed CR or PR (by IRC) to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone.
• CR rate – defined as the proportion of subjects who achieve a confirmed CR (by IRC)
• Progression-free survival (PFS) – defined as the interval from the first dose of study drug to the first documentation of definitive disease progression or death from any cause
• MRD negativity rate – defined as the proportion of subjects with MRD <10^-4, assessed by flow cytometry in bone marrow at Week 36 (+4
weeks) after therapy initiation. For subjects receiving the final dose of rituximab after the original scheduled date, the MRD assessment will be performed no fewer than 12 weeks after the last dose of rituximab.
• Nodal response rate – defined as the proportion of subjects who achieve a 50% decrease from baseline in the sum of the products of the
greatest perpendicular diameters (SPD) of index lesions
• Overall survival (OS) – defined as the interval from the first dose of study drug to death from any cause |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Primary analysis will be performed when all enrolled subjects have completed efficacy, safety, and other assessments through ≥36 weeks of evaluation. The final analysis will be performed at the conclusion of the study. |
|
| 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 | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | No |
| 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.8.3 |
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 | 68 |
| 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 |
| Australia |
| Austria |
| Belgium |
| Bulgaria |
| Canada |
| Czech Republic |
| Denmark |
| France |
| Hungary |
| Italy |
| Poland |
| Portugal |
| Romania |
| Spain |
| Switzerland |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 10 |
| 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 | 10 |
| 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 |
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