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MEK Inhibitor 162 Relapsed and/or Refractory Acute Myeloid Leukemia (AML) and Poor Prognosis, Not Suitable for or Unwilling to Receive Standard Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02089230
Recruitment Status : Completed
First Posted : March 17, 2014
Last Update Posted : October 25, 2019
Sponsor:
Collaborator:
Array BioPharma
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of MEK162 that can be given to patients with advanced leukemia.

This is an investigational study. MEK162 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.

Up to 57 patients total will take part in both phases of this study . All will be enrolled at MD Anderson.

The goal of Phase 2 of this clinical research study is to learn if MEK162 can help to control AML in older patients with advanced leukemia. The safety of this drug will also be studied.

This is an investigational study. MEK162 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.

Up to 57 patients total will take part in both phases of this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Leukemia Drug: MEK 162 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of MEK Inhibitor MEK162 in Patients With Relapsed and or Refractory Acute Myeloid Leukemia and Patients With Poor Prognosis Acute Myeloid Leukemia Not Suitable for or Unwilling to Receive Standard Therapy
Actual Study Start Date : August 27, 2014
Actual Primary Completion Date : June 5, 2019
Actual Study Completion Date : June 5, 2019


Arm Intervention/treatment
Experimental: MEK 162

Phase I Starting Dose of MEK 162: 15 mg by mouth twice a day in a 28 day cycle.

Phase II Starting Dose of MEK 162: Maximum tolerated dose from Phase I.

Drug: MEK 162

Phase I Starting Dose of MEK 162: 15 mg by mouth twice a day in a 28 day cycle.

Phase II Starting Dose of MEK 162: Maximum tolerated dose from Phase I.





Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of MEK 162 in Participants with Advanced Leukemias [ Time Frame: 28 days ]
    Maximum tolerated dose is the highest dose level in which <2 patients of 6 develop dose limiting toxicity (DLT).


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Assessed after one 28-day cycle of treatment ]
    Overall response rate is number of participants with response of CR or CRi according to International Working Group (IWG) consensus criteria for treatment response in Acute Myeloid Leukemia (AML) (modified): Morphological Complete Remission (CR): Normalization of the peripheral blood absolute neutrophil count > 1.0x109/L, platelets > than 100x109/L no residual evidence of extramedullary disease and bone marrow aspirate with ≤ 5% blasts, no blasts with Auer rods (AML only); and Morphological Complete Remission with incomplete blood count recovery (CRi): Same as CR but without normalization of the peripheral blood absolute neutrophil and platelet count.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. PHASE I -- a. Primary or secondary AML according to WHO classification, with relapsed or refractory disease or newly diagnosed older subjects (greater than or equal to 65 years of age), not candidates for intensive chemotherapy; b. Subjects with MDS, IPSS Int-2 or high risk (RAEB-2 only, i.e. greater than or equal to 10% blast) who are resistant or intolerant to standard treatment and are not candidates for transplantation; c. Subjects with ALL, relapsed, refractory or intolerant to standard treatment and for whom no effective treatment options are available.
  2. Age greater or equal to 18 years.
  3. Patients should be willing and able to give informed consent.
  4. Eastern Cooperative Group (ECOG) PS less than or equal to 2.
  5. PHASE II -- Patients aged 60 and older with newly diagnosed primary or secondary AML according to WHO classification, without any prior therapy for AML with the exception of (a) emergency Leukapheresis and (b) emergency treatment for hyperleukocytosis with hydroxyurea that is allowed until 24 hours before start of the trial treatment. Note: Prior therapy for preexisting hematological condition e.g. MDS or MPD, including but not limited to hypomethylating agents is allowed until at least 2 weeks have elapsed from completion of that agent before the first dose of MEK 162.
  6. Patients must meet at least one of the following conditions: a. Age greater than or equal to 75 years; b. Age greater or equal to 60 and less than 75 years with at least one of the following poor prognostic factors: i. Secondary AML, as determined by known and documented exposure to chemotherapy or radiation therapy; ii. antecedent history of MDS or myeloproliferative disorder according to WHO criteria for at least 3 months prior to trial entry; iii. unfavorable cytogenetic abnormalities including chromosome 5 and 7 as well as complex; iv. ECOG Performance status 2. (Phase II ONLY)
  7. Patients are willing and able to give informed consent. (Phase II only)
  8. Only patients with mutated RAS (KRAS and NRAS) mutations are eligible to participate. (Phase II only)
  9. Adequate cardiac function defined as: --left ventricular ejection fraction (LVEF) greater than or equal to 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram; -- QTcF interval less than or equal to 480 ms. (Phase II only)

Exclusion Criteria:

  1. PHASE I and II -- Administration of any antineoplastic therapy within at least 4 weeks (cytotoxic chemotherapy) or 2 weeks (biological and targeted therapy; hypomethylating agents are considered to be biological therapy) of that therapy of the first MEK 162/MEK 162 dose; except the use of hydroxyurea which can be administered up to 5 g/day up to 24 hours before the initiation of the study drug.
  2. Patients should not have received an investigational agent for at least 2 weeks prior to the first study drug dose.
  3. Clinical evidence of active CNS leukemia requiring active therapy; prior CNS leukemia well-controlled by ongoing therapy is allowed.
  4. Active and uncontrolled infection including but not limited to known infection with HIV, active hepatitis B, or hepatitis C.
  5. Major surgery within two weeks prior to trial entry.
  6. Liver function tests above the following limits at the screening: total bilirubin > 1.5 x ULN unless related to Gilbert's syndrome or hemolysis, AST and/or ALT > 2.5 X ULN, or for subjects with liver involvement AST and/or ALT > 5 x ULN.
  7. Serum creatinine > 1.5 x ULN and/or Creatinine Clearance (CrCl) < 30 mL/min at screening (calculation according to Cockcroft & Gault formula).
  8. Pregnant or nursing (lactating) women;
  9. Female patients of childbearing potential and male patients with partners of childbearing potential who are not willing ot use highly effective methods of contraception throughout the study and for 1 month after study drug discontinuation. Highly effective contraception methods include: **Total abstinence; or **Male or female sterilization; **Combination of any two of the following (a+b or a+c or b+c); a. Use of oral, injected, or implanted hormonal methods of contraception; b. Placement of an intrauterine device (IUD) or intrauterine system (IUS); c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
  10. Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at screening;
  11. History of significant difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the tested product.
  12. Has significant cardiac conduction abnormalities and/ or pacemaker or any of the following criteria: -- History of acute coronary syndromes (including myocardial infarction, unstable angina, CABG, coronary angioplasty, or stenting) <6 months prior to screening, --Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening --Uncontrolled arterial hypertension, defined as BP > 140/100 mmHg (average of 3 consecutive readings)
  13. History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO).
  14. Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes).
  15. Subjects with active other tumors, except early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN).
  16. Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  17. Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment.
  18. Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02089230


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Array BioPharma
Investigators
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Principal Investigator: Farhad Ravandi-Kashani, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02089230    
Other Study ID Numbers: 2013-0116
NCI-2014-01518 ( Registry Identifier: NCI CTRP )
First Posted: March 17, 2014    Key Record Dates
Last Update Posted: October 25, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute Myeloid Leukemia
AML
Advanced leukemias
Myelodysplastic syndrome
MDS
Acute lymphoblastic leukemia
ALL
Relapsed
Refractory
MEK 162
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms