MDACC Study Summary 2007-0096

Study Summary
No. 2007-0096:.......Leukemia......William G. Wierda......Leukemia

Study Summary Title



Study Summary Number:	2007-0096

Study Title:	A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects with Relapased or Refractory Chronic Lymphocytic Leukemia

Physician

New Patient Referral



Name:	William G. Wierda	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Leukemia	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-745-0428 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	Abbott Laboratories

Phase of Study:	Phase I/Phase II	Return Visit:	Eval. on C1D1, 2, 3, 4, 5, 6, 8, 14 and 16, then on Day 1, 3, 5, 8, 14, 15 and 16 of subsequent courses. Eval. on D1, 2, 3, 5 and 7 of lead-in period of 21/21 day dose sched. There is a 30 day safety visit. Then every 3 mo for 2 yr for pts in Ph 2a

Treatment Agents:	ABT-263	Home Care:	This is an oral agent that will be self-administered daily at home.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	NA

Description/
Intervention:

The goal of the Phase I portion of this clinical research study is to find the
highest tolerable dose of ABT-263 that can be given to patients with CLL that
has come back or did not get better after earlier treatment. The safety of this
drug in treating chronic lymphocytic leukemia is also studied. Researchers will
also perform pharmacokinetic (PK) testing of the ABT-263. PK testing measures
the amount of study drug in the body at different time points.

Study Objectives / Outcomes

Phase 1
- Safety assessment
- Dose limiting toxicity (DLT) determination
- Maximum tolerated dose (MTD) determination
- Recommended Phase 2 Dose (RPTD) and schedule determination
- Pharmacokinetic profile evaluation

Phase 2a
- Safety assessment at the recommended Phase 2 dose (RPTD) and schedule
- Preliminary efficacy assessment including biomarker assessment
- Pharmacokinetic profile evaluation

Study Status Information



Study Activation / Registration Date:	07/02/2007

IRB Review and Approval Date:	07/02/2007

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	68; Phase 1=36; Phase 2a=32

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Phase 1 Inclusion Criteria. The subject must be >/= 18 years of age.

2) The subject must have relapsed or refractory CLL 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) Subject must have adequate bone marrow, independent of growth factor support (with the exception of subjects with ANC <1000/microliter and bone marrow heavily infiltrated with underlying disease [80% or more]), renal and hepatic function, per local laboratory reference range at Screening as follows: - Bone marrow: Absolute Neutrophil count (ANC) >/= 1000/microliter; Platelets >/= 75,000/mm^3 (entry platelet count must be independent of transfusion within 14 days of Screening).

6) Continued from above Inclusion: Hemoglobin >/= 9.0 g/dL; Renal Function:Serum creatinine </= 2.0 mg/dL or calculated creatinine clearance >/= 50 mL/min; Hepatic Function and enzymes: AST and ALT </= 3.0 x the upper normal limit (ULN) of institution's normal range; Bilirubin </= 1.5 x ULN. Subjects with Gilbert's Syndrome may have a Bilirubin >1.5 x ULN; - Coagulation: aPTT, PT, not to exceed 1.2 x ULN.

7) Female subjects must be surgically sterile, postmenopausal (for at least one year), or have negative results for a pregnancy test performed as follows: - At Screening on a serum sample obtained within 14 days prior to initial study drug administration, and - Prior to dosing on a urine sample obtained on Lead-in Day 1 (lead-in period) if it has been > 7 days since obtaining the serum pregnancy test results.

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 following methods of birth control: - total abstinence from sexual intercourse (minimum one complete menstrual cycle); - a vasectomized partner; - hormonal contraceptives (oral, parenteral or transdermal) for at least three months prior to study drug administration; - double-barrier method (including condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream).

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.

10) Phase 2a Inclusion Criteria. The subject must be >/= 18 years of age.

11) The subject must have CLL and require treatment in the opinion of the investigator.

12) The subject has relapsed disease and has received no more than 5 prior myelosuppressive/chemotherapy regimens.

13) Subject has an Eastern Cooperative Oncology Group performance score of </=1.

14) 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.

15) The subject must have adequate bone marrow, independent of growth factor support (with the exception of subjects with ANC < 1000/microliter and bone marrow heavily infiltrated with underlying disease [80% or more]), renal and hepatic function, per local laboratory reference range at Screening as follows: - Bone marrow: Absolute Neutrophil count (ANC) >/= 1000/microliter; Platelets >/= 75,000/mm^3 (entry platelet count must be independent of transfusion within 14 days of Screening); Hemoglobin >/= 9.0 g/dL; - Renal function: Serum creatinine </= 2.0 mg/dL or

16) Continued from above Inclusion Criteria: - calculated creatinine clearance >/= 50 mL/min; Hepatic function and enzymes: AST and ALT </= 3.0 x the upper normal limit (ULN) of institution's normal range; Bilirubin </= 1.5 x ULN. Subjects with Gilbert's Syndrome may have a Bilirubin > 1.5 x ULN; - Coagulation: aPTT, PT must not exceed 1.2 x ULN.

17) Female subjects must be surgically sterile, postmenopausal (for at least one year), or have negative results for a pregnancy test performed as follows: - At Screening on a serum sample obtained within 14 days prior to initial study drug administration, and - Prior to dosing on a urine sample obtained on Cycle 1 Day 1 or Lead-in Day 1 if it has been > 7 days since obtaining the serum pregnancy test results.

18) 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 following methods of birth control: - total abstinence from sexual intercourse (minimum one complete menstrual cycle); - a vasectomized partner; - hormonal contraceptives (oral, parenteral or transdermal) for at least three months prior to study drug administration; - double-barrier method (including condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream).

19) 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.

Exclusion Criteria:

1) Phase 1 Exclusion Criteria. The subject has a history or is clinically suspicious for cancer-related Central Nervous System (CNS) disease.

2) The subject has undergone an allogeneic or autologous stem cell transplant.

3) 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.

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 had received aspirin within seven days prior to the first dose of study drug.

7) The subject is currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that effect platelet function, with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter.

8) The subject has received steriod 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.

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 1 week prior to study drug administration

17) Phase 2a Exclusion Criteria. The subject has a history or is clinically suspicious for cancer-related Central Nervous System (CNS) disease.

18) 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.

19) The subject has undergone an allogeneic or autologous stem cell transplant.

20) The subject has active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis.

21) 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).

22) The subject is currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that effect platelet function, with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter.

23) The 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.

24) The subject has received aspirin within seven days prior to the first dose of study drug.

25) 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(s) of the previous therapy.

26) The subject has received a biologic within 30 days prior to the first dose of study drug.

27) The subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.

28) 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.

29) A female subject is pregnant or breast-feeding.

30) 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 potentially drug-drug interactions with certain anti-infective agents).

31) 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.

32) 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.

33) The subject has received known CYP3A inhibitors (e. g. ketoconazole) within 7 days prior to first dose of study drug.

Links

Registration Number: NCT00481091
Study Information on Clinical Trials Registry (clinicaltrials.gov)