Study to Assess Safety, Tolerability and Preliminary Efficacy of BKM120, PI3K Kinase Inhibitor, With Advanced Leukemias

NCT01396499 | Completed Phase 1

• 2 other identifiers: 2010-0874NCI-2011-01610
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of BKM 120

  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. Toxicity assessed using the NCI Common Toxicity Criteria for Adverse Events, version 4.0.

  28 days, Cycle 1

Study Arms (1)

BKM120

EXPERIMENTAL

Oral BKM120 starting dose 80 mg once daily.

Drug: BKM120

Interventions

BKM120 DRUG

Starting dose 80 mg tablets by mouth daily for a 28 day cycle.

BKM120

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years old or older
• Relapsed/refractory leukemias for which no standard therapy options are anticipated to result in a durable remission: Acute myelogenous leukemia (AML) by World Health Organization (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 \[inv16, t(8;21)\].
• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2
• 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.
• Fasting glucose =/\< 120 mg/dL (6.7 mmol/L).
• Total calcium (corrected for serum albumin) within normal limits (8.8 - 10.5 MG/DL). This is MD Anderson Cancer Center (MDACC) lab standard. Supplements for calcium allowed to meet eligibility criteria.
• Magnesium \>/= the lower limit of normal (1.8 MG/DL). Supplements for magnesium allowed to meet eligibility criteria
• Potassium within normal limits (3.5 - 5.0 milliequivalent (MEq)/L). Supplements for potassium allowed to meet eligibility criteria
• international normalized ratio (INR) =/\< 2
• 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
• Patients should be able to take oral medications.

You may not qualify if:

• 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).
• Patients who have received targeted anticancer therapy ≤ 2 week (for non myelosuppressive therapy) prior to starting study drug.
• central nervous system (CNS) disease
• 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), corrected QT interval (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
• 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
• 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, diffusion capacity of lung for carbon monoxide (DLco), O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates.
• Patient has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus
• Patients with acute or chronic liver, renal disease or pancreatitis
• Patients with diarrhea \>/= CTCAE grade 2
• 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
• 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
• 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
• Patients who have received prior treatment with a PI3K inhibitor
• Patients with a known hypersensitivity to BKM120 or to its excipients
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Marina Konopleva, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2011
• First Posted: July 18, 2011
• Study Start: July 1, 2012
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: November 1, 2016

Record last verified: 2016-10

Locations

US (1)