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A Phase I Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of BKM120, PI3K Kinase Inhibitor, in Patients With Advanced Leukemias

Phase 1
18 Years
Open (Enrolling)

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Trial Information

A Phase I Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of BKM120, PI3K Kinase Inhibitor, in Patients With Advanced Leukemias

The Study Drug:

BKM120 is designed to block a protein that is important to the growth and division of cancer
cells, which may cause the cells to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of BKM120 based on when you join this study. Up to 2 dose levels of BKM120 will be
tested. Up to six (6) participants will be enrolled at each dose level. The first group of
participants will receive the lower dose level.

You will take BKM120 tablets by mouth with a large glass of water every day you are on this
study. You should take BKM120 about 1 hour after a light breakfast. You should take BKM120
at about the same time each day. You need to fast (not eat or drink anything except water)
for 2 hours after you take your BKM120 dose.

You should swallow the BKM120 tablets whole. The tablets must not be chewed, broken, or
crushed. If you vomit after taking BKM120, you should not take another tablet that day to
make up for that dose. If you forget to take BKM120 one morning, call your doctor and ask
for instructions. Do not take BKM120 after 6pm of the same day or take any extra doses to
make up for the missed dose.

If your study doctor feels it is needed or if you have side effects, BKM120 may be stopped
and then started again at a lower dose or may be stopped completely.

You will be asked to record in a pill diary each dose you take. You will return the pill
diary, unused study drug, and pill containers to the clinic staff at the end of each cycle.

Study Visits:

On this study, each study cycle will last 28 days. You will have study visits every other
week (Days 1 and 15) during the first 2 cycles of the study, and then once a month after
that. The following tests and procedures will be performed at all study visits:

- Your medical history will be recorded

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- You will be asked about any drugs you may be taking and about any side effects you may
be having.

- Blood (about 1 tablespoon) will be drawn for routine tests and to check your blood
sugar. You will need to fast for 8 hours before this blood draw.

- You will complete the questionnaires about your mood.

On Day 28 of Cycle 1 and every 3 months after that, you will have a bone marrow aspirate
and/or biopsy to check the status of the disease. You may have additional bone marrow
aspirations collected while you are on study if the doctor thinks they are needed.

Every 4 months, you will have a MUGA scan or an ECHO to check the status of the disease.

ECGs and chest x-rays may be performed throughout the study to check your heart and lung
function if the doctor thinks they are needed.

Length of Study:

You may continue taking the study drug for as long as 12 cycles if the doctor thinks it is
in your best interest. You will no longer be able to take the study drug if the disease
gets worse, if intolerable side effects occur, or if you are unable to follow study

Your participation on the study will be over once you have completed the end-of-study visit.

End-of-Study Visit:

After you stop taking BKM120, you will have an end-of-study visit. The following tests and
procedures will be performed:

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- You will be asked about any drugs you may be currently taking or have taken.

- You will complete the questionnaires about your mood.

- Blood (about 1 tablespoon) and urine will be collected for routine tests. The blood
will also be used to check your kidney and liver function and to check your blood
sugar. You will need to fast for 8 hours before this blood draw.

- You will have a MUGA scan or an ECHO to check the status of the disease.

- You will have a bone marrow aspirate and/or biopsy to check the status of the disease.

This is an investigational study. BKM120 is not FDA approved or commercially available. It
is currently being used for research purposes only.

Up to 16 patients take part in this study. All will be enrolled at MD Anderson.

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 promyelocytic
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

4. Serum total bilirubin 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
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

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 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
myelosuppressive 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) 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 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose of BKM 120

Outcome Description:

Maximum tolerated dose (MTD) defined as highest dose in which 1/6 or less subjects experience a dose limiting toxicity (DLT) during the first course of treatment.

Outcome Time Frame:

28 days, Cycle 1

Safety Issue:


Principal Investigator

Marina Konopleva, MD, PHD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2012

Completion Date:

Related Keywords:

  • Leukemia
  • Leukemia
  • Acute leukemias
  • Relapsed/refractory leukemias
  • Acute myelogenous leukemia
  • AML
  • Acute lymphoblastic leukemia
  • ALL
  • BKM120
  • Leukemia



UT MD Anderson Cancer Center Houston, Texas  77030