E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Chronic Lymphocytic Leukemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008978 |
E.1.2 | Term | Chronic lymphocytic leukemia refractory |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008976 |
E.1.2 | Term | Chronic lymphocytic leukemia |
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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 objectives of the Phase 1 portion of the study include: ● Safety assessment ● Dose limiting toxicity (DLT) determination ● Maximum tolerated dose (MTD) determination ● Pharmacokinetic profile evaluation
The objectives of the Phase 2a portion of the study include: ● Safety assessment at the recommended Phase 2 dose (RPTD) and schedule determination ● Preliminary efficacy assessment including biomarker assessment ● Pharmacokinetic profile evaluation
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E.2.2 | Secondary objectives of the trial | |
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 |
Biomarker sub-study as part of main study protocol, version 29 April 2008: Several putative biomarkers of efficacy and response will be evaluated to define the relationship between drug concentration and disease status.
Pharmacogenetic sub-study as part of main study protocol, version 29 April 2008: DNA samples may be analyzed for genetic factors contributing to the subject's response to ABT-263 in terms of pharmacokinetics and safety and may also be used for the development of a diagnostic test for drug response.
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E.3 | Principal inclusion criteria |
Phase 1 Inclusion Criteria A subject will be eligible for study participation if he/she meets the following criteria:
1. The subject must be ≥ 18 years of age. 2. The subject must have alemtuzumab-refractory CLL or relapsed or refractory CLL with contraindications against the use of alemtuzumab and require treatment in the opinion of the investigator. 3. The subject has an Eastern Cooperative Oncology Group performance score of ≤ 1. 4. Subjects receiving Selective Serotonin Reuptake Inhibitor (SSRI) anti-depressants (e.g., Prozac) must be receiving a stable dose for at least 21 days prior to the first dose of study drug. 5. The subject must have adequate bone marrow, renal and hepatic function. Please see protocol for more information. 6. Female subjects must be surgically sterile, postmenopausal (for at least one year), or have negative results for a pregnancy test. Please see protocol for more information. 7. All female subjects not surgically sterile or postmenopausal (for at least one year) and non-vasectomized male subjects must practice at least one of the methods of birth control described in the protocol. 8. The subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
Phase 2a Inclusion Criteria A subject will be eligible for study participation if he/she meets the following criteria:
1. The subject must be ≥ 18 years of age. 2. The subject must have CLL and require treatment in the opinion of the investigator. 3. The subject has alemtuzumab-refractory disease or the subject has relapsed disease with contraindications against the use of alemtuzumab and has received no more than 5 prior myelosuppressive/chemotherapy regimens (see Section 5.1). 4. Subject has an Eastern Cooperative Oncology Group performance score of ≤ 1. 5. Subjects receiving Selective Serotonin Reuptake Inhibitor (SSRI) anti-depressants (e.g., Prozac) must be receiving a stable dose for at least 21 days prior to the first dose of study drug. 6. The subject must have adequate bone marrow independent of growth factor support (with the exception of subjects with ANC < 1000/μL and bone marrow heavily infiltrated with underlying disease [80% or more]), renal and hepatic function, per local laboratory reference range at Screening as follows: 7. Female subjects must be surgically sterile, postmenopausal (for at least one year), or have negative results for a pregnancy test. Please see protocol for more information. 8. All female subjects not surgically sterile or postmenopausal (for at least one year) and non-vasectomized male subjects must practice at least one of the methods of birth control described in the protocol. 9. The subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
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E.4 | Principal exclusion criteria |
Phase 1 and Phase 2a Exclusion Criteria A subject will not be eligible for study participation if he/she meets any of the following criteria:
1. The subject has a history or is clinically suspicious for cancer-related Central Nervous System (CNS) disease. 2. The subject has a recent history (within 1 year prior to first dose of study drug) of an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding. 3. The subject has undergone an allogeneic or autologous stem cell transplant. 4. The subject has active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis. 5. The subject has active immune thrombocytopenic purpura or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug). 6. The subject is currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter. 7. Subject has received steroid therapy for anti-neoplastic intent within seven days prior to the first dose of study drug with the exception of inhaled steroids for asthma, topical steroids or replacement/stress corticosteroids. 8. The subject has received aspirin within seven days prior to the first dose of study drug. 9. The subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for thyroid conditions or estrogen replacement therapy [ERT]), or any investigational therapy within 14 days prior to the first dose of study drug, or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of the previous therapy. 10. The subject has received a biologic within 30 days prior to the first dose of study drug. 11. The subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug. 12. The subject has a significant history of cardiovascular disease (e.g., myocardial infarction [MI] thrombotic, or thromboembolic event in the last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study. 13. A female subject is pregnant or breast-feeding. 14. The subject has tested positive for HIV (due to potential drug-drug interactions between anti-retroviral medications and ABT-263, as well as anticipated ABT-263 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections and potential drug-drug interactions with certain anti-infective agents). 15. The subject has a history of other active malignancies within the past 3 years prior to study entry, with the exception of: ● adequately treated in situ carcinoma of the cervix uteri; ● basal or squamous cell carcinoma of the skin; ● previous malignancy confined and surgically resected with curative intent. 16. The subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: ● uncontrolled systemic infection (viral, bacterial, or fungal); ● diagnosis of fever and neutropenia within one week prior to study drug administration. 17. The subject has received known CYP3A inhibitors (e.g., ketoconazole) within 7 days prior to first dose of study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 |
A Phase 1/2a Study Evaluating Safety, Pharmacokinetics and Efficacy |
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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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 |
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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
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Defined in the Protocol as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |