E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
B Cell Chronic Lymphocytic Leukemia |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Lymphocytic Leukemia |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008956 |
E.1.2 | Term | Chronic lymphatic leukaemia |
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 |
To evaluate the efficacy of ABT-263 when given according to two different regimens in combination with dose-intense rituximab in previously untreated patients with B-cell CLL, as measured by progression-free survival (PFS) based on investigator assessments |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of dose-intense, rituximab monotherapy in previously
untreated patients with B-cell CLL
• To evaluate the efficacy of ABT-263 when given according to two different
regimens in combination with dose-intense rituximab in previously untreated
patients with B-cell CLL
• To compare the pharmacokinetics of ABT-263 and rituximab when administered
alone to that when the two therapies are administered in combination
• To investigate the effects of rituximab on the pharmacokinetics of ABT-263
and the effects of ABT-263 on rituximab pharmacokinetics
• To evaluate the efficacy of rituximab monotherapy either alone or when
administered with ABT-263 according to two different regimens in previously
untreated patients with B-cell CLL
• To evaluate the safety and tolerability of ABT-263 when given according to
two different regimens in combination with dose-intense rituximab in
previously untreated patients with B-cell CLL |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Predictive biomarker studies - refer section 3.2.4 of the protocol
2. Pharmacogenomic studies - refer section 3.2.5 of the protocol
Subjects who agree to participate in these sub-studies are required to sign additional informed consent documentation. |
|
E.3 | Principal inclusion criteria |
Inclusion Criteria:
Previously untreated, CD20-positive B-cell CLL
ECOG performance status of 0 or 1
Life expectancy > 6 months
Willingness and capability to be accessible for follow-up until study termination or death
For patients of reproductive potential (both males and females), use of a reliable means of contraception |
|
E.4 | Principal exclusion criteria |
Exclusion Criteria:
Prolymphocytic leukemia
Richter's transformation to an aggressive B-cell malignancy (e.g., DLBCL)
Prior radiotherapy to a lesion(s) that will be used to assess response unless that lesion(s) shows clear evidence of progression at baseline
Patients with a history of other malignancies within 2 years prior to study entry except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin carcinoma, low-grade, localized prostate cancer treated surgically with curative intent or one that carries a good prognosis, in situ ductal carcinoma of the breast treated with lumpectomy alone with curative intent
Prior treatment with rituximab, ABT-263 or other pro-apoptotic agents
Current or recent (within the 28 days prior to initiation of study treatment) participation in another experimental drug study
Major surgical procedure (excluding lymph node biopsy) or significant traumatic injury within 28 days prior to treatment onset or anticipation of the need for major surgery during the course of the study
Active infection requiring parenteral antibiotics or antiviral or antifungal agents at the onset of study treatment
Receipt of primary or booster vaccination with live-virus vaccines for up to 6 months prior to initiation of study treatment
Patients receiving therapeutic anticoagulation with heparin or warfarin or patients receiving any drugs or herbal supplements that are known to inhibit platelet function (including low-dose aspirin) within 7 days of the first dose of ABT-263. Note: Patients receiving low-dose anticoagulation for the purpose of maintaining central venous catheter patency are eligible.
Patients who have an inherited or acquired bleeding diathesis, including (but not limited to) hemophilia or immune or thrombotic thrombocytopenic purpura, or who have had an underlying condition that predisposes to abnormal bleeding (e.g., peptic ulcer disease) within 1 year prior to the first dose of ABT-263
Patients with a history of refractoriness to platelet transfusions
Clinically significant cardiovascular disease
Known human immunodeficiency virus (HIV) infection, seropositivity for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody or RNA
Pregnancy or breastfeeding
Concurrent (or within 7 days prior to the first dose of study treatment) systemic corticosteroid therapy except some low-dose corticosteroid therapies
History of other disease, metabolic dysfunction, physical or laboratory finding(s) giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, might affect interpretation of the results of the study or render the patient at high risk from treatment complications
History of anaphylaxis, allergic reaction, or hypersensitivity to sulfites (sodium metabisulphite is included in study drug formulation)
Any contraindication to alcohol ingestion (study drug formulation includes approximately 15% ethanol) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is PFS, defined as the time from randomization to
the first occurrence of progression or relapse (as defined in Appendix E of the protocol) as assessed by the investigator or death on study. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time Frame: From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from First Patient In [FPI]) |
|
E.5.2 | Secondary end point(s) |
Overall response rate (ORR) [ Time Frame: Approximately 40 months from FPI ]
Duration of response [ Time Frame: Approximately 40 months from FPI ]
Complete response (CR) rate [ Time Frame: Approximately 40 months from FPI ]
Progression-free survival as assessed by a blinded, independent review [ Time Frame: From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from FPI) ]
ORR as assessed by a blinded, independent review [ Time Frame: Approximately 40 months from FPI ]
Duration of response as assessed by a blinded, independent review [ Time Frame: Approximately 40 months from FPI ]
CR rate as assessed by a blinded, independent review [ Time Frame: Approximately 40 months from FPI ]
Overall survival (OS) [ Time Frame: From randomization until death due to any cause (approximately 4 years after Last Patient In) ] |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Approximately 40 months from FPI |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 29 |
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 | Information not present in EudraCT |
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 |
Brazil |
Israel |
Russian Federation |
Ukraine |
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
|
The end of the trial is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer. |
|
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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |