E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Lymphocytic Leukemia 17 p Deletion |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of the blood and 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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024340 |
E.1.2 | Term | Leukemia lymphocytic chronic |
E.1.2 | System Organ Class | 100000004864 |
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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-199 monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. Efficacy will be measured by overall response rate (ORR). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the duration of response, progression free survival (PFS), time to progression (TTP), overall survival (OS) and percent of subjects who move on to stem cell transplant. The safety and tolerability of ABT-199 in subjects with relapsed or refractory CLL harboring 17p deletion will also be evaluated. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must be ≥ 18 years of age
2. Subject must have diagnosis of CLL that meets published 2008 IWCLL NCI-WG criteria.
• Subject has an indication for treatment according to the 2008 IWCLL NCI-WG criteria;
• Subject has clinically measurable disease;
• Subject must have relapsed or be refractory after receiving at least one prior line of therapy (a line of therapy is defined as completing at least 2 cycles of treatment for a given line of therapy);
• Subjects must have 17p deletion, assessed by central laboratory, and determined by FISH using the Vysis CLL probe kit.
3. Subject has an ECOG performance score of ≤ 2
4. Subjects must meet the following laboratory parameters, per laboratory reference range: ANC ≥ 1000/µL-For subjects with an ANC < 1000/μL at Screening and bone marrow heavily infiltrated with underlying disease (approximately 80% or more), G-CSF may be administered after Screening and prior to the first dose of ABT-199 to achieve the ANC eligibility criteria (≥ 1000/μL); Platelet count > 40,000 mm3, (independent of
transfusion within 14 days of screening); aPTT and PT ≤ 1.5 × ULN; Hemoglobin ≥ 8.0 g/dL; AST and ALT ≤ 3 × ULN; Calculated creatinine clearance> 50 mL/min; Total bilirubin ≤ 1.5 × ULN (Subjects with Gilbert's Syndrome may have bilirubin > 1.5 × ULN with the approval of the Abbott medical monitor).
5. For high risk subjects (as defined in Section 6.7.1) a pre approval by the AbbVie medical monitor is required prior to enrollment. |
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E.4 | Principal exclusion criteria |
1. Subject has undergone an allogeneic stem cell transplant or has developed Richter's transformation.
2. Subject has received a biologic agent (i.e. monoclonal antibodies) for anti-neoplastic intent within 8 weeks prior to the first dose of study drug. Subject has received any anti-cancer therapy including chemotherapy, or radiotherapy; Investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug, or has not recovered to less than CTC grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
3. Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study. For subjects who have required an intervention for any above diseases within the past 6 months a discussion with the investigator and the AbbVie medical monitor must occur. 4. Exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal).
5. History of other active malignancies other than CLL within the past 3 years prior to study entry, with the following exceptions: Adequately treated in situ carcinoma of the cervix uteri; Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
6. Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks), including autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP).
7. Subject has tested positive for HIV due to potential drug-drug interactions as well as anticipated mechanism-based lymphopenia that may increase the risk of
opportunistic infections.
8. Cardiovascular disability status of New York Heart Association Class ≥2.
9.Subject has known allergy to both xanthine oxidase inhibitors and rasburicase. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every month through Week 36, then every 3 months thereafter. Survival data will be collected every 3 months for a period of 5 years after the subject has enrolled in the study. |
|
E.5.2 | Secondary end point(s) |
Complete remission rate (CR), partial remission rate (PR), duration of response, progression free survival (PFS), time to progression (TTP), overall survival (OS) and percent of subjects who move on to stem cell transplant. The safety and tolerability of ABT-199 in subjects with relapsed or refractory CLL harboring 17p deletion will also be evaluated. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every month through Week 36, then every 3 months thereafter. The safety and tolerability of ABT-199 will be assessed at every study visit through the safety follow up period. Survival data will be collected every 3 months for a period of 5 years after the subject has enrolled in the study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | 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 | 20 |
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 |
Canada |
France |
Germany |
Poland |
Ukraine |
United Kingdom |
United States |
|
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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |