Clinical trial NCT01116128 (phase 2, status: terminated)
Conditions: myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: dasatinib, melphalan, prednisone
SMILES: CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1, N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O, [H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C
Reason stopped: 
    difficulty in enrolling patients
  
Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 18 years and ≤75 year

          2. Karnofsky performance status ≥ 60%

          3. Patient is, in the investigator(s) opinion, willing and able to comply with the
             protocol requirements.

          4. Patient has given voluntary written informed consent before performance of any
             study-related procedure not part of normal medical care, with the understanding that
             consent may be withdrawn by the patient at any time without prejudice to their future
             medical care.

          5. Patient of reproductive potential must agree to use and utilize an adequate method of
             contraception throughout treatment and for at least 4 weeks after study drug is
             stopped.

          6. Patient was previously diagnosed with symptomatic MM based on standard criteria, and
             has measurable disease, defined as follows:

               -  Secretory myeloma: any quantifiable serum monoclonal protein value (generally,
                  but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5
                  g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of >200
                  mg/24 hours;

               -  Non-secretory myeloma: > 30% plasma cells in the bone marrow and at least one
                  plasmocytoma > 2 cm as determined by clinical examination or applicable
                  radiographs (i.e., MRI or CT scan).

          7. Patient is relapsed or refractory and has received previous regimen containing
             Thalidomide or Lenalidomide and Bortezomib or even MP (patient is refractory if there
             is a progression during the last therapy or within 2 months after its completion).

          8. Patient has a life-expectancy > 3 months

          9. Patient has ≤ Grade 2 peripheral neuropathy within 28 days before enrollment and all
             acute toxicities from any prior therapy (radiotherapy, chemotherapy or surgical
             procedures) must have resolved to grade ≤ 2, according to the NCI CTCAE version 3.0 at
             study entry.

         10. Patient has the ability to take oral medication (dasatinib must be swallowed whole)

         11. Concomitant Medications:

             - Patient agrees that IV bisphophonates will be withheld for the first 8 weeks of
             Dasatinib therapy due to risk of hypocalcemia.

         12. Patient has the following laboratory values within 28 days before Baseline day 1 of
             the Cycle 1:

               -  Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN)

               -  Hepatic enzymes (AST, ALT ) ≤ 2.5 times the institutional ULN

               -  Serum Na, K+, Mg2+, Phosphate and Calcium > Lower Limit of Normal (LLN)

               -  Calculated or measured creatinine clearance: ≥ 20 mL/minute

               -  Hemoglobin, Neutrophil count, Platelets, PT, PTT, Fibrinogen all Grade 0-1

               -  Corrected serum calcium ≤ 14 mg/dL ( ≤ 3.5 mmol/L).

        Exclusion Criteria:

          1. Patients with > 2 previous treatment regimens.

          2. Multiple myeloma treatment (ie, chemotherapy, biological, immunotherapy or
             investigational agent [therapeutic or diagnostic]) administered within 21 days prior
             to treatment initiation.

          3. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          4. Pregnant or breast feeding females.

          5. Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          6. Use of any other concomitant standard/experimental anti-myeloma drug or therapy

          7. Concurrent anticoagulation treatment or medications that directly or durably inhibit
             platelet function.

          8. Malignancy [other than the one treated in this study] which required radiotherapy or
             systemic treatment within the past 5 year. Exceptions: basal cell or non metastatic
             squamous cell carcinoma of the skin, cervical carcinoma in situ or FIGO Stage 1
             carcinoma of the cervix.

          9. Concurrent medical condition which may increase the risk of toxicity, including:

             - Pleural or pericardial effusion of any grade

         10. Clinically significant cardiac disease (NYHA classification III and IV); any of the
             following should be considered for exclusion:

               1. Uncontrolled angina, congestive heart failure or MI within (6 months)

               2. Diagnosed congenital long QT syndrome

               3. Any history of clinically significant ventricular arrhythmias (such as
                  ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)

               4. Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)

               5. Subjects with hypokalemia or hypomagnesemia, if it cannot be corrected prior to
                  dasatinib administration.

         11. History of significant bleeding disorder unrelated to cancer, including:

               1. Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

               2. Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
                  VIII antibodies)

               3. Ongoing or recent (< 3 months) significant gastrointestinal bleeding.

         12. Concomitant Medications, any of the following should be considered for exclusion:

               1. Category I drugs that are generally accepted to have a risk of causing Torsades
                  de Pointes including: (Patients must discontinue drug 7 days prior to start
                  dasatinib)

                    -  quinidine, procainamide, disopyramide

                    -  amiodarone, sotalol, ibutilide, dofetilide

                    -  erythromycin, clarithromycin

                    -  chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide,
                       zyprasidone

                    -  cisapride, bepridil, droperidol, methadone, arsenic, chloroquine,
                       domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin,
                       lidoflazine.

               2. 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. If antacid
                  therapy is needed, the antacid dose should be administered at least 2 hours prior
                  to or 2 hours after the dose of dasatinib.

               3. Patient may not be receiving any prohibited CYP3A4 inhibitors (see Section 8.6
                  Prohibited therapies-). Refer to Section Prohibited therapies for other
                  concomitant medications you may wish to prohibit based on disease/patient
                  population.

         13. Women who:

               1. 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

               2. have a positive pregnancy test at baseline, or

               3. are pregnant or breastfeeding. 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.

         14. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (e.g., infectious) illness.

         15. Patient that assume anti-arrhythmic drugs or other medicinal products which led to QT
             prolongation and cumulative high dose anthracycline.

         16. Patient has active infectious hepatitis type B or C or HIV.

         17. Patient has known intolerance to lactose