Return to List

Study Summary
No. 2009-0239:.......Leukemia......Gautam Borthakur......Leukemia
.
Study Summary Title
Study Summary
Number:
2009-0239
Study Title:An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor GSK1120212 in Subjects with Relapsed or Refractory Leukemias
.
Physician New Patient Referral
Name:Gautam BorthakurPatients 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:713-563-1586
Contact us about clinical trials
.
General Information
Disease Group:LeukemiaSupported By:GlaxoSmithKline
Phase of Study:Phase I/Phase IIReturn
Visit:
Every 4 weeks while on study.
Treatment
Agents:
GSK1120212Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of Phase 1 of this clinical research study is to find the highest
tolerable dose of GSK1120212 that can be given to patients with leukemia. The
safety of this drug will also be studied.
.
Study Objectives / Outcomes
Phase I
Primary:
1. To determine the safety, tolerability and recommended Phase II dose and regimen of GSK1120212 given orally.
Secondary:
1. To characterize the pharmacokinetics (PK) of GSK1120212 after single- and repeat-dose administration.
2. To evaluate the pharmacodynamics (PD) response after treatment with GSK1120212.
Translational:
1. To determine the association of clinical and PK endpoints with genetic and protein profiles from bone marrow and blood.

Phase II
Primary:
1. To evaluate clinical efficacy after treatment with GSK1120212.
Secondary:
1. To characterize the PK of GSK1120212 after single- and repeat-dose administration.
Translational:
1. To correlate clinical activity with DNA mutations.
.
Study Status Information
Study Activation / Registration Date:07/03/2009
IRB Review and Approval Date:06/04/2009
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:Phase 1: 30; Phase II: 45
.
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) Phase I: Sign a written informed consent.

2) 18 years old or older.

3) Subjects must have relapsed/refractory leukemias for which no standard therapies are anticipated to result in a durable remission. Subjects with poor-risk myelodysplasia (MDS) [i.e. refractory anemia with excess blasts (RAEB-1 or RAEB-2) by WHO classification] and chronic myelomonocytic leukemia (CMML) are also eligible. Relapsed/refractory leukemias include acute non-lymphocytic leukemia (AML) by WHO classification, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML) in blast crisis.

4) #3 continued: Subjects with agnogenic myeloid metaplasia (AMM) are also eligible.

5) Subjects >/= 60 years of age with AML who are not candidates for or have refused standard chemotherapy.

6) Subjects who have previously received an autologous stem cell transplant are allowed if a minimum of three months has elapsed from the time of transplant (T0) and the subject has recovered from transplant-associated toxicities prior to the first dose of GSK1120212.

7) Subjects with a history of allogeneic stem cell transplant are eligible for study participation provided the following eligibility criteria are met: *transplant was greater than 100 days prior to study enrollment; *subject has not taken immunosuppressive medications (including but not limited to: cyclosporine, tacrolimus, methotrexate, or mycophenolate mofetil) for at least one month; *no signs or symptoms of graft versus host disease other than Grade 1 skin involvement; *no active infection; *subject meets the remainder of the eligibility criteria outlined in the protocol.

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

9) Life expectancy of at least four weeks

10) Able to swallow and retain oral medication

11) Male subjects must agree to use one of the contraception methods listed: abstinence; condom plus spermicidal agent (foam/gel/film/cream/suppository). This criterion must be followed from the time of the first dose of study medication until four weeks after the last dose of study medication. However, the Sponsor advised that contraception be used for a total of 16 weeks following the last dose (based on the lifecycle of sperm).

12) A female subject is eligible to participate if she is of 1)Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post menopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/mL and estradiol less than 40 pg/mL (greater than 140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods as described:

13) #11 continued: Abstinence; intrauterine device (IUD) or intrauterine system (IUS) that meets the less than 1% effectiveness criteria as stated in the product label; male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, "documented" refers to the outcome of the investigator's/designee's medical examination of the subject or review of the subject's medical history for study eligibility,

14) #11 continued: as obtained via a verbal interview with the subject or from the subject's medical records; double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least two to four weeks will elapse between the cessation of therapy and the blood draw;

15) #11 continued: this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. 2)Child-bearing potential and agrees to use one of the contraception methods listed above for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until four weeks after the last dose of study medication.

16) Calcium phosphate product less than or equal to 4.0 mmol^2/L^2 (50 mg^2/dL^2).

17) Adequate organ system function

18) Phase II: as for Phase I, except replace #3 with the following: Histologically or cytologically confirmed diagnosis of relapsed or refractory AML.

Exclusion Criteria:1) Haematological malignancy associated with human immunodeficiency virus (HIV) infection or solid organ transplant.

2) Concurrent malignancy of solid tumors.

3) Currently receiving cancer therapy (chemotherapy, radiation therapy, immuno- therapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization). Note: For proliferative disease, hydroxyurea will be allowed during Week 1 and 2.

4) Received corticosteroids or imatinib within 24h of GSK1120212 administration.

5) Received gemtuzumab ozogamicin (myelotarg) within two weeks of GSK1120212 adminstration.

6) Received an investigational anti-cancer drug within four weeks or five half-lives, whichever is shorter of GSK1120212 administration--as long as a minimum of 14 days has passed between the last dose of the prior investigational anti-cancer drug and the first dose of GSK1120212.

7) Received major surgery, radiotherapy, or immunotherapy within four weeks of GSK1120212 administration.

8) Received chemotherapy regimens with delayed toxicity within the last four weeks (six weeks for prior nitrosourea or mitomycin C). Received chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last two weeks. Note: Use of hematopoetic growth factors is permitted at the discretion of the investigator according to published guidelines (e.g. NCCN, ASCO, ASH etc.).

9) Received a MEK inhibitor.

10) Current use of a prohibited medication or requires any of these medications during treatment with GSK1120212.

11) Current use of anticoagulants (e.g. warfarin, heparin) at therapeutic levels within seven days prior to the first dose of GSK1120212. Low dose (prophylactic) low molecular weight heparin (LMWH) is permitted provided that subject's PT and PTT meet entry criteria. Subjects requiring therapeutic levels of LMWH must receive approval from GSK Medical Monitor and be monitored appropriately as clinically indicated.

12) Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.

13) History of retinal vein occlusion, central serous retinopathy or glaucoma.

14) Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein occlusion or central serous retinopathy.

15) Intraocular pressure > 21mm Hg as measured by tonography.

16) Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

17) Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.

18) Symptomatic or untreated central nervous system (CNS) involvement by the hematologic malignancy (including primary CNS lymphoma). Subjects who were previously treated for CNS involvement, and are asymptomatic without anti-epileptic medications for at least two months are eligible.

19) Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease).

20) Unresolved toxicity greater than common terminology criteria for adverse events (CTCAE) Grade 1 from previous anti-cancer therapy except alopecia (if applicable) unless agreed to by a GlaxoSmithKline (GSK) Medical Monitor and the investigator.

21) Corrected QT interval on electrocardiogram (QTc) interval greater than or equal to 480 msecs.

22) History of acute coronary syndromes (including unstable angina), coronary angioplasty or stenting within the past 24 weeks.

23) Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.

24) Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, dimethyl sulfoxide (DMSO), or excipients (To date there are no known FDA approved drugs chemically related to GSK1120212).

25) Pregnant or lactating female.

26) Unwillingness or inability to follow the procedures outlined in the protocol.

.
Links
Registration Number: NCT00920140
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
.
Results


Return to Clinical Trials at M.D. Anderson Cancer Center