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Study Summary
No. 2011-0164:.......Leukemia......William G. Wierda......Leukemia
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Study Summary Title
Study Summary
Number:
2011-0164
Study Title:A Phase 1 Study Evaluating the Safety and
Pharmacokinetics of ABT-199 in Subjects with Relapsed or Refractory
Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma
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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
Phase of Study:Phase IReturn
Visit:
Treatment
Agents:
ABT-199 Home Care:
Treatment Loc:Both at MDACC & and Other Sites
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of ABT-199 that can be given patients with relapsed or refractory CLL, NHL, or
SLL. The safety of this drug will also be studied.

ABT-199 is designed to block a critical protein that the leukemia cells need to
survive, which may kill cancer cells and shrink tumors. This is the first study
using ABT-199 in humans.
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Study Objectives / Outcomes
The primary objectives of this study are to assess the safety profile, characterize pharmacokinetics (PK), determine the maximum tolerated dose (MTD), determine the recommended phase 2 dose (RPTD), and determine the lead-in period regimen of ABT-199 in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Food effect will be studied in the NHL dose escalation portion of the study.

The secondary objectives are to evaluatae preliminary efficacy data regarding the effect of ABT-199 on progression-free survival (PFS), objective response rate (ORR), time to tumor progression (TTP), overall survival (OS), and duration of response. Biomarkers and pharmacogenetics will also be evaluated as secondary objectives.
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Study Status Information
Study Activation / Registration Date:04/05/2012
IRB Review and Approval Date:04/05/2012
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:118
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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) Arm A - Relapsed or refractory CLL/SLL Subject requires treatment in the opinion of the investigator. Subject must have relapsed following or be refractory to standard treatments such as fludarabine based regimens (F, FC, FR, FCR) or alkylator (chlorambucil, bendamustine) based regimens. In addition, the subject is unable to tolerate other available therapies or no other therapies are available. or Arm B - Relapsed or refractory non-Hodgkin lymphoma Subject must have histologically documented diagnosis of a non- Hodgkin lymphoma as defined in the World Health Organization (WHO) classification scheme, except as noted in Exclusion Criteria. Subject must have relapsed following or be refractory to standard treatments such as R-CHOP, RCVP, or fludarabine based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care. Subjects with other lymphoproliferative diseases can be considered.

3) Subject has an ECOG performance score of </= 1.

4) Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening as follows: ● Absolute Neutrophil Count (ANC) >/= 1000/micro L; ○ An exception is for subjects with an ANC < 1000/micro L and bone marrow heavily infiltrated with underlying disease (approximately 80% or more) may use growth factor to achieve the ANC eligibility criteria per discussion with the Abbott medical monitor; ● Platelets >/= 50,000/mm3 (entry platelet count must be independent of transfusion within 14 days of Screening); ● Hemoglobin >/= 9.0 g/dL.

5) Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows: aPTT and PT not to exceed 1.2 × ULN; Calculated creatinine clearance >/= 50 mL/min; AST and ALT </= 3.0 × the upper normal limit (ULN) of institution's normal range; Bilirubin </= 1.5 × ULN. Subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN, per discussion between the investigator and Abbott medical monitor.

6) Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test performed as follows: ● At Screening on a serum sample obtained within 14 days prior to the first study drug administration, and ● Prior to dosing on a urine sample obtained on Week 1 Day –3 (dose escalation phase) or Week 1 Day 1 (expanded safety cohort) if it has been > 7 days since obtaining the serum pregnancy test results.

7) All female subjects not surgically sterile or postmenopausal (for at least 1 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, transdermal, or vaginal ring) for at least 3 months prior to study drug administration; ● Double-barrier method (including condoms plus diaphragm or vaginal cup with spermicide, contraceptive sponge, jellies or cream).

8) 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.

9) NHL 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 that is 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) >/= 1,500/µL; ● Platelets >/= 75,000/mm3 (entry platelet count must be independent of transfusion within 14 days of Screening; ● Hemoglobin >/= 10.0 g/dL

Exclusion Criteria:1) Subject has undergone an allogeneic or autologous stem cell transplant.

2) Subject has tested positive for HIV (due to potential drug-drug interactions between anti-retroviral medications and ABT-199, as well as anticipated ABT-199 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections and potential drug-drug interactions with certain anti-infective agents).

3) Subject requires the use of warfarin.

4) Subject has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.

5) Subject has received any of the following 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: ● Any anti-cancer therapy including chemotherapy, or radiotherapy; ● Investigational therapy, including targeted small molecule agents.

6) Subject has received the following within 7 days prior to the first dose of study drug: ● Steroid therapy for anti-neoplastic intent; ● CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin; ● CYP3A inducers such as carbamazepine, phenytoin, and St. John's wort.

7) Subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.

8) Subject has a history of a prior significant toxicity from another Bcl-2 family protein inhibitor.

9) Subject has a cardiovascular disability status of New York Heart Association Class >/= 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain.

10) Subject has a significant history of 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) A female subject is pregnant or breast-feeding.

12) Subject has a history of other active malignancies other than CLL within the past 3 years prior to study entry, with the exception of: ● 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 with curative intent.

13) Subject has malabsorption syndrome or other condition which precludes enteral route of administration.

14) 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.

15) NHL subject has undergone an allogeneic stem cell transplant.

16) NHL subject has been diagnosed with Post-Transplant Lymphoproliferative Disease (PTLD), Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia.

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Links
Registration Number: NCT01328626
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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