A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia.
- Conditions
- Relapsed or Refractory Chronic Lymphocytic LeukemiaMedDRA version: 9.1Level: LLTClassification code 10008978Term: Chronic lymphocytic leukemia refractoryMedDRA version: 9.1Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemia
- Registration Number
- EUCTR2007-002143-25-DE
- Lead Sponsor
- Abbott GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 72
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: ;Primary end point(s): Safety Assessment;Main Objective: The objectives of the Phase 1 portion of the study include:<br>?Safety assessment<br>?Dose limiting toxicity (DLT) determination<br>?Maximum tolerated dose (MTD) determination<br>?Pharmacokinetic profile evaluation<br><br>The objectives of the Phase 2a portion of the study include:<br>?Safety assessment at the recommended Phase 2 dose (RPTD) and schedule determination<br>?Preliminary efficacy assessment including biomarker assessment<br>? Pharmacokinetic profile evaluation<br>
- Secondary Outcome Measures
Name Time Method