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Study Summary
No. 2009-0077:.......Leukemia......William G. Wierda......Leukemia
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Study Summary Title
Study Summary
Number:
2009-0077
Study Title:A Phase I Study Evaluating the Safety of ABT-263 in Combination with Either Fludarabine/Cyclophosphamide/Rituximab (FCR) or Bendamustine/Rituximab (BR) in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia
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Physician New Patient Referral
Name:William G. WierdaPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring 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
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General Information
Disease Group:LeukemiaSupported By:Abbott Laboratories
Phase of Study:Phase IReturn
Visit:
ARM A- Eval. Cyc. 1& 2, D 1-8, 15 & 22. Cyc.3, D1-3, 15 & 22. Subsequent Cyc.,
D 1-3, 8, 15, &22.
ARM B- Eval. Cyc. 1 D 1-8, 15 &22. Cyc. 2&3, D 1-3, 8, 15 & 22. Subsequent
Cyc., D1-3, 8, 15 & 22
Treatment
Agents:
ABT-263
Bendamustine HCl
Cyclophosphamide
Fludarabine
Rituximab
Home Care:Treatment will be administered at the MDACC ATC infusion units.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
Treatment will be administered on an outpatient basis
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of ABT-263 (navitoclax) that can be given in combination with bendamustine and
rituximab to patients with relapsed or refractory CLL. Researchers also want to
learn more about how the study drug is broken down and absorbed by the body.
The safety of this drug combination in treating CLL will also be studied.
Researchers also want to learn about biomarkers (substances in the blood that
may be related to your reaction to the study drug).
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Study Objectives / Outcomes
Primary:
Safety assessment
Pharmacokinetic characterization
Maximum tolerated dose (MTD) determination
Recommended Phase 2 Dose (RPTD) determination

Secondary:
Evaluate preliminary data regarding progression-free survival (PFS), objective response rate (ORR),
time to tumor progression, overall survival (OS), duration of response and ECOG status when ABT-263 is administered in combination with either FCR or BR.
Biomarker assessment
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:11/19/2009
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:36
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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) Subject must be >/= 18 years of age.

2) The subject must have relapsed or refractory CLL, received no more than 5 prior myelosuppressive/chemotherapy regimens and must be a candidate for treatment with either FCR or BR.

3) The subject has an Eastern Cooperative Oncology Group performance score of </= 1.

4) Subjects receiving Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants (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 measurable disease according to NCI-WG criteria.

6) The subject must have adequate bone marrow independent of any growth factor support (with the exception of subjects with bone marrow heavily infiltrated with underlying disease [80% or more] who may use growth factor support to achieve ANC eligibility criteria) per laboratory reference range at Screening as follows: Absolute Neutrophil count (ANC)>/= 1000/microliter; Platelets >/= 100,000/mm^3 (entry platelet count must be independent of transfusion within 14 days of Screening); Hemoglobin >/= 9.0 g/dL.

7) Subjects who have a history of an autologous stem cell transplant (e.g.,bone marrow) must be > 6 months post transplant (prior to the first dose of study drug) and have adequate bone marrow independent of any growth factor support (with the exception of subjects with bone marrow heavily infiltrated with underlying disease [80% or more] who may use growth factor support to acheive ANC eligibility criteria) per laboratory reference range at Screening as follows:

8) Continued from above criteria - Absolute Neutrophil count (ANC) >/= 1500/microliter; Platelets >/= 125,000/mm^3 (entry platelet count must be independent of transfusion within 14 days of Screening; Hemoglobin >/= 10.0 g/dL.

9) 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 if it has been > 7days since obtaining the serum pregnancy test results.

10) 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).

11) 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.

12) The subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows: 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.

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

2) Subject has a history of severe allergic or anaphylactic reactions to human, humanized, chimeric or murine monoclonal antibodies.

3) The subject has undergone an allogeneic stem cell transplant.

4) 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.

5) The subject had an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding.

6) The subject has a recent history of non-chemotherapy induced thrombocytopenic associated bleeding (within 6 months 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 active immune thrombocytopenic purpura or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug).

9) Subject has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.

10) 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.

11) Female subject is pregnant or breast-feeding.

12) Subject has tested positive for Hepatitis B or Hepatitis C.

13) 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).

14) Subject has a history of other active malignancies within three 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; in situ carcinoma of the bladder; previous malignancy confined and surgically resected with curative intent.

15) The subject has a history of prior toxicity from fludarabine, cyclophophamide, or rituximab if enrolling on Arm A or bendamustine or rituximab if enrolling on Arm B that resulted in permanent discontinuation of treatments.

16) Subject has prior significant toxicity from ABT-263.

17) Subject has received immunization with live vaccine within 6 months prior to first dose of study drug.

18) The subject has received antibody therapy (except rituximab) within 30 days prior to the first dose of study drug.

19) The subject has received any anti-cancer therapy, including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for thyroid conditions or estrogen replacement [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.

20) The subject has received steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of study drug. Exception of steroid use includes inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids.

21) Subject has received aspirin within 7 days prior to the first dose of study drug.

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

23) Any subdural hematoma.

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

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Links
Registration Number: NCT00868413
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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