Clinical Trials /

UARK 2014-08 A Phase II Open-Label, Multiple-Dose, Single Agent Study to Evaluate the Overall Response Rate of Orally Administered Trametinib

NCT02140840

Description:

The purpose of this study is to evaluate the overall response rate of Trametinib when administered orally to patients with relapsed or refractory multiple myeloma

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: UARK 2014-08 A Phase II Open-Label, Multiple-Dose, Single Agent Study to Evaluate the Overall Response Rate of Orally Administered Trametinib
  • Official Title: A Phase II Open-Label, Multiple-Dose, Single Agent Study to Evaluate the Overall Response Rate of Orally Administered Trametinib in Patients With Relapsed of Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 202550
  • NCT ID: NCT02140840

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
TrametinibMekinist, TMTB, JTP-74057, JTP-78296, JTP-75303

Purpose

The purpose of this study is to evaluate the overall response rate of Trametinib when administered orally to patients with relapsed or refractory multiple myeloma

Detailed Description

      The effect of on tumor response will be determined using the International Myeloma Working
      Group uniform response criteria by analyzing changes in serum and urine values of monoclonal
      protein immunoglobulin kappa and lambda free light chain and ratio, microglobulin, lactate
      dehydrogenase, hemoglobin and C-reactive proten.
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

          -  Been identified as having multiple myeloma with activating NRAS, KRAS or BRAF genetic
             mutations on CD138+ cells, identified by molecular genetic testing

          -  Have been diagnosed with multiple myeloma by having met all three of the following
             IMWG criteria:

        a Clonal bone marrow plasma cells >10% b Presence of serum and/or urinary M-protein (If no
        monoclonal protein is detected (non-secretory disease), then >/= 30% monoclonal bone marrow
        plasma cells and/or a biopsy-proven plasmacytoma required.) c Evidence of end-organ damage
        that can be attributed to the underlying plasma cell proliferative disorder, specifically,
        one or more of the following: (i) Hypercalcemia: serum calcium >11.5 mg/100 mL (ii) Renal
        insufficiency: serum creatinine >2 mg/dL (iii) Anemia: normochromic, normocytic with a
        hemoglobin value >2 g/100 mL below the lower limit of normal or a hemoglobin value <10
        g/100 mL (iv)Bone lesions: lytic lesions, severe osteopenia, or pathologic fracture.

          -  Have measurable disease defined by the following:

             (i) Serum M-protein ≥1g/dL or urine M-protein ≥200 mg/24 hours by protein
             electrophoresis (ii) If neither serum nor urine M-protein meet the criteria above,
             then kappa or lambda serum FLC must be ≥10 mg/dL accompanied by an abnormal kappa to
             lambda ratio (<0.26 or >1.65) (Serum FLC should only be used for patients without
             measurable serum or urine M-protein spike.)

          -  Have relapsed or refractory disease after two or more prior multiple myeloma treatment
             regimens, each of which may have consisted of either single or multiple therapies

          -  Be at least 3 weeks beyond the last multiple myeloma therapy and have recovered from
             acute toxicities of prior therapies measured by CTCAE Ver 3.0.

          -  Have an Eastern Cooperative Oncology Group performance status of 0 to 2

          -  Have life expectancy of at least 3 months

          -  Be ≥18 years of age and willing to provide written informed consent

          -  For women of childbearing potential, must have used effective contraceptive methods
             for previous 4 weeks and agree to continue using such methods during the study and for
             at least 4 months after completing the study, this must include the use of a
             male/female latex barrier method of contraception (for male participants (See APPENDIX
             K). TMTB is a pregnancy category D drug. A female of childbearing potential is defined
             as a female who has not been in natural menopause for the previous, consecutive 24
             months, or undergone hysterectomy or bilateral oophortectomy. Women of childbearing
             potential must have a negative serum pregnancy test within 24 hours before the
             initiation of TMTB therapy.

          -  Have an absolute neutrophil count >1,000/mm3

          -  Have a platelet count >50,000/mm3

          -  Have total direct bilirubin <2.0 mg/dL

          -  Have aspartate aminotransferase and alanine aminotransferase ≤3 times the upper limit
             of normal

          -  Have serum creatinine ≤2.5 times the upper limit of normal

          -  Have hemoglobin ≥8.5 g/dL

          -  All prior treatment- related toxicities must be CTCAE (Version 3.0) ≤ Grade 1 (except
             alopecia)

          -  Subject is able to swallow and retain orally administered medication and does not have
             any clinically significant gastrointestinal abnormalities that may alter absorption
             such as malabsorption syndrome or major resection of the stomach or bowels

        Exclusion Criteria:

          -  Have an active infection or serious comorbid medical condition

          -  Be receiving other concurrent anticancer agents or therapies

          -  Be receiving other concurrent investigational therapies or have received
             investigational therapies within 3 weeks of screening, not inclusive of molecular
             genetic testing

          -  Be eligible to receive any other standard therapy available that is known to extend
             life expectancy

          -  For women be pregnant, nursing, unwilling or unable to utilize two forms of birth
             control, including the use of a latex condom.

          -  Have a history of another malignancy, except as noted below Exception: Subjects who
             have been disease-free for 3 years, or subjects with a history of completely resected
             non-melanoma skin cancer and/or subjects with indolent second malignancies are
             eligible.

          -  Any serious and/or unstable pre-existing medical disorder (aside from malignancy
             exception above), psychiatric disorder, or other conditions that could interfere with
             subject's safety, obtaining informed consent or compliance to the study procedures.

          -  History of interstitial lung disease or pneumonitis.

          -  Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).

          -  Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity,
             biologic therapy, or immunotherapy within 21 days prior to randomization and/or daily
             or weekly chemotherapy without the potential for delayed toxicity within 14 days prior
             to randomization.

          -  History of retinal vein occlusion (RVO)

          -  Symptomatic or untreated spinal cord compression.

          -  Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C
             Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and HCV
             infection will be permitted).

          -  History or evidence of cardiovascular risk including any of the following (See
             APPENDIX M for more details):

        a LVEF<LLN b A QT interval of ≥ 480 msec corrected for heart rate using the Bazett's
        formula (QTcB;).

        c History or evidence of current clinically significant uncontrolled arrhythmias.

        Exception: Subjects with controlled atrial fibrillation for >30 days prior to study
        enrollment d History of acute coronary syndromes (including myocardial infarction and
        unstable angina), coronary angioplasty, or stenting within 6 months prior to study
        enrollment

        * History or evidence of current ≥ Class II congestive heart failure as defined by New York
        Heart Association (NYHA).

        a Treatment refractory hypertension defined as a blood pressure of systolic> 140 mmHg
        and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy; b
        Patients with intra-cardiac defibrillators; c Known cardiac metastases
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The response rate of Trametinib when administered orally to patients with relapsed multiple myeloma
Time Frame:28 day
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:University of Arkansas

Trial Keywords

  • TMTB
  • Mekinist
  • Trametinib
  • relapse
  • refractory
  • response rate

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