A Phase II Study of Dasatinib in the Treatment of Relapsed or Plateau Phase Multiple Myeloma
Condition: Relapsed, Refractory or Plateau Phase Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dasatinib
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Dasatinib; Plateau phase

Summary:

      To evaluate the response rate (Complete Response [CR] and Partial Response [PR]) to dasatinib
      in patients with relapsed, refractory or plateau phase multiple myeloma whose serum
      paraprotein levels are >0.5g/dL or urine paraprotein levels are >1.0g/24 hours.
    

Eligibility criteria:

        Inclusion Criteria

          -  Multiple myeloma diagnosed by standard criteria with either relapsed or plateau-phase
             disease.

               -  Relapsed: At least 1 prior therapy for multiple myeloma with documented evidence
                  of progression on the most recent treatment.

               -  Plateau-phase: subjects with myeloma who had a response to their most recent
                  multiple myeloma therapy (including autologous transplantation or other
                  investigational agents) and have residual detectable monoclonal protein in their
                  serum or urine that has been stable for greater than or equal to 3 months (+/-
                  25% change in M-protein).

          -  Measurable levels of monoclonal protein in serum (greater than or equal to 0.5 g/dL)
             or urine (greater than or equal to 1.0 g/24 hr).

          -  Age 18 years or older.

          -  ECOG performance status of less than or equal to 2.

          -  Acceptable organ and marrow function as defined below:

               -  Hemoglobin of greater than or equal to 8 gm/dL

               -  Absolute neutrophil count of greater than or equal to 500/mm3

               -  Platelets of greater than or equal to 50,000/mm3

               -  PT and PTT of less than or equal to 1.5 times the institutional Upper Limit of
                  Normal (ULN)

               -  Total bilirubin of less than or equal to 2.0 times the institutional ULN
                  institutional ULN

               -  Hepatic enzymes (AST, ALT ) equal to 2.5 times the institutional ULN

               -  Serum Na, K+, Mg2+, Phosphate and Ca2+ greater than or equal to Lower Limit of
                  Normal (LLN)

               -  Serum Creatinine of less than or equal to 1.5 times the institutional ULN

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Ability to take oral medication (dasatinib must be swallowed whole)

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (sensitivity of less than or equal to 25IU HCG/L) within 72 hours prior to the
             start of study drug administration

          -  Persons of reproductive potential must agree to use an adequate method of
             contraception throughout treatment and for at least 4 weeks after study drug is
             stopped.

          -  Signed written informed consent including HIPAA according to institutional guidelines.

        Exclusion Criteria

          -  Receiving any of the following therapies or medications:

               -  Any investigational agents within 30 days.

               -  Drugs that are generally accepted to have a risk of causing Torsade de Pointes
                  including:

               -  quinidine, procainamide, disopyramide

               -  amiodarone, sotalol, ibutilide, dofetilide

               -  erythromycin, clarithromycin

               -  chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

               -  cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,

               -  halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine

               -  Subjects who have discontinued any of these medications must have a wash-out
                  period of at least 7 days prior to the first dose of dasatinib.

               -  Medications known to be potent CYP3A4 inhibitors (See Appendix D).

               -  The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is
                  not recommended. The use of antacids should be considered in place of H2 blockers
                  or proton pump inhibitors in patients receiving dasatinib therapy (See section
                  5.5.2.3 for important cautions regarding use of antacids.)

               -  Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy.

               -  Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of
                  dasatinib therapy due to risk of hypocalcemia.

               -  Prior therapy with dasatinib

          -  Biopsy proven amyloidosis.

          -  History of other malignancy (except for basal cell or squamous cell carcinoma of the
             skin or carcinoma in situ of the cervix or breast) which required radiotherapy or
             systemic treatment within the past 5 years.

          -  Concurrent medical condition which may increase the risk of toxicity, including:

               -  Pleural or pericardial effusion of any grade

               -  Clinically-significant coagulation or platelet function disorder (e.g. known von
                  Willebrand's disease)

          -  Cardiac Symptoms or Cardiovascular Disease, including:

               -  Myocardial infarction within 6 months

               -  Uncontrolled angina within 6 months

               -  Congestive heart failure within 6 months

               -  Diagnosed or suspected congenital long QT syndrome

               -  Any history of clinically significant ventricular arrhythmias (such as
                  ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes). Any
                  subject with a history of any arrhythmia should be discussed with the
                  Investigator prior to entry into the study.

               -  Prolonged QTc interval on pre-entry electrocardiogram (greater than 450 msec) on
                  Bazett's correction. However, if Bazett's correction is high (i.e., greater than
                  450 msec) and Fridericia is less than or equal to 450 msec, the subject is
                  eligible.

               -  Subjects with hypokalemia or hypomagnesemia if it cannot be corrected

          -  Dementia or altered mental status that would prohibit the understanding or rendering
             of informed consent

          -  History of significant bleeding disorder unrelated to cancer, including:

               -  Diagnosed congenital bleeding disorder (e.g., von Willebrand's disease)

               -  Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
                  VIII antibodies)

               -  Ongoing or recent (less than or equal to 3 months) significant gastrointestinal
                  bleeding

          -  Women:

               -  are unwilling or unable to use an acceptable method to avoid pregnancy for the
                  entire study period and for at least 4 weeks after cessation of study drug, or

               -  have a positive pregnancy test at baseline, or

               -  are breastfeeding.

          -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious) illness

        Sexually active women of childbearing potential (WOCBP) must use an effective method of
        birth control during the course of the study, in a manner such that risk of failure is
        minimized.

        Prior to study enrollment, women of childbearing potential must be advised of the
        importance of avoiding pregnancy during trial participation and the potential risk factors
        for an unintentional pregnancy.

        All WOCBP MUST have a negative pregnancy test prior to first receiving dasatinib. If the
        pregnancy test is positive, the patient must not receive dasatinib and must not be enrolled
        in the study.