Dasatinib in Combination With Melphalan and Prednisone to Treat Relapsed and Refractory Multiple Myeloma Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01116128
• Date of registration: 17/03/2010
• Primary sponsor: Fondazione Neoplasie Sangue Onlus
• Public title: Dasatinib in Combination With Melphalan and Prednisone to Treat Relapsed and Refractory Multiple Myeloma Patients D-MP
• Scientific title: A Multicenter, Open-label, Phase Ii Study of Dasatinib in Combination With Melphalan and Prednisone (D-MP) in Advanced, Relapsed / Refractory Multiple Myeloma Patients
• Date of first enrolment: February 2008
• Target sample size: 8
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT01116128
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Italy

Contacts

• Name: Mario Boccadoro, MD
• Affiliation: Divisione Universitaria di Ematologia Ospedale Molinette di Torino

Key inclusion & exclusion 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consent may be withdrawn by the patient at any time without prejudice to their future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


Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Myeloma

Intervention(s)

Drug: dasatinib

Drug: melphalan

Drug: prednisone

Primary Outcome(s)

Partial response rate is a primary study endpoint. [Time Frame: 4 years]

Secondary Outcome(s)

Secondary objectives are progression-free survival and overall survival [Time Frame: 4 years]

Secondary ID(s)

CA180-210

Source(s) of Monetary Support

Please refer to primary and secondary sponsors