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Study Summary
No. 2010-0874:.......Leukemia......Marina Konopleva......Leukemia
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Study Summary Title
Study Summary
Number:
2010-0874
Study Title:A Phase I Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of BKM120, PI3K kinase inhibitor, in Patients with Advanced Leukemias
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Physician New Patient Referral
Name:Marina KonoplevaPatients 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:713-794-1628
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:Novartis
Phase of Study:Phase IReturn
Visit:
Treatment
Agents:
BKM120Home Care:
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of BKM120 that can be given to patients with relapsed or refractory leukemia.
The safety of BKM120 will also be studied.
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Study Objectives / Outcomes

Primary:

1. To determine the dose limiting toxicity and maximum tolerated dose of BKM 120 in patients with acute leukemias

Secondary:
1. To determine the safety and tolerability of BKM120
2. To determine clinically relevant disease responses with BKM120
3. To determine the effect of BKM120 on biomarkers of PI3K/mTOR signaling

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Study Status Information
Study Activation / Registration Date:07/23/2012
IRB Review and Approval Date:07/23/2012
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:N/A
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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) Age 18 years old or older

2) Relapsed/refractory leukemias for which no standard therapy options are anticipated to result in a durable remission: Acute myelogenous leukemia (AML) by WHO classification or acute lymphoblastic leukemia (ALL) relapsed or refractory to standard chemotherapy; unsuitable for standard chemotherapy or unwilling to undergo standard chemotherapy. Philadelphia chromosome (Ph) positive ALL eligible if failed prior tyrosine-kinase inhibitor therapy. Age =/> 60 years with AML not candidates for or have refused standard chemotherapy, excluding subjects with acute promyelcytic leukemia (APL) or with favorable cytogenetic abnormalities [inv16, t(8;21)].

3) Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2

4) Serum total bilirubin </= 2 x ULN or direct bilirubin </=ULN for patients with total bilirubin levels > 2 x ULN, unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis. Aspartate aminotransferase or alanine aminotransferase within normal range (or =/< 3.0 x upper limit of normal (ULN) if due to leukemic involvement); serum creatinine =/< 1.5 x ULN or 24-hour clearance =/> 50 mL/min; serum amylase </= ULN; serum lipase</= ULN.

5) Fasting glucose =/< 120 mg/dL (6.7 mmol/L).

6) Total calcium (corrected for serum albumin) within normal limits (8.8 - 10.5 MG/DL). This is MDACC lab standard. Supplements for calcium allowed to meet eligibility criteria.

7) Magnesium >/= the lower limit of normal (1.8 MG/DL). Supplements for magnesium allowed to meet eligibility criteria

8) Potassium within normal limits (3.5 - 5.0 MEq/L). Supplements for potassium allowed to meet eligibility criteria

9) international normalized ratio (INR) =/< 2

10) Women of childbearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum or urine pregnancy test within 48 hours prior to the start of study drug

11) Patients should be able to take oral medications.

Exclusion Criteria:1) Patients who have received myelosuppressive chemotherapy </= to 4 weeks prior to starting study drug (with the exception of Hydroxyurea which will be allowed during Course 1 of treatment).

2) Patients who have received targeted anticancer therapy ≤ 2 week (for non myelosuppresive therapy) prior to starting study drug.

3) central nervous system (CNS) disease

4) Patient has active cardiac disease including any of the following: Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO), QTc > 480 msec on screening ECG (using the QTcF formula), Angina pectoris that requires the use of anti-anginal medication, Ventricular arrhythmias except for benign premature ventricular contractions, Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication, Conduction abnormality requiring a pacemaker, Valvular disease with document compromise in cardiac function, Symptomatic pericarditis

5) Patient has a history of cardiac dysfunction including any of the following: Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function Documented congestive heart failure (New York Heart Association functional classification III-IV) Documented cardiomyopathy

6) Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., e.g., uncontrolled infection, such as persistent fever despite antibacterial therapy) that could cause unacceptable safety risks or compromise compliance with the protocol. Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates.

7) Patient has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus

8) Patients with acute or chronic liver, renal disease or pancreatitis

9) Patients with diarrhea >/= CTCAE grade 2

10) Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with unresolved diarrhea will be excluded as previously indicated

11) Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) </= 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued

12) Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: a. Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) b. >/= CTCAE grade 3 anxiety c. Meets the cut-off score of >/= 10 in the Patient Health Questionnaire PHQ-9 or a cut-off of >/= 15 in the General Anxiety Disorder GAD-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study unless overruled by the psychiatric assessment

13) Patients who have received prior treatment with a PI3K inhibitor

14) Patients with a known hypersensitivity to BKM120 or to its excipients

15) Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug. Please refer to table 4-7 or a list of prohibited QT prolonging drugs with risk of Torsades de Pointes

16) Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. If treatment with such an inhibitor is in the best interest of the patient, extreme caution should be taken with its concomitant use. Please refer to Table 4-6 for a list of prohibited inhibitors and inducers of CYP3A (Please note that co-treatment with weak inhibitors of CYP3A is allowed)

17) Patients receiving chronic treatment with steroids or another immunosuppressive agent

18) Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits

19) Patients who have undergone major surgery </= 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

20) Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant

21) Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control. Double barrier contraceptives must be used through the trial by both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of child-bearing potential must have a negative serum or urine pregnancy test ≤ 48 hours prior to initiating treatment.

22) Known diagnosis of human immunodeficiency virus (HIV) infection

23) History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix and squamous cell carcinoma in situ of the skin.

24) Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator

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Links
Registration Number: NCT01396499
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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