MyelomaPhase 2D-MPNCT01116128
Dasatinib in Combination With Melphalan and Prednisone to Treat Relapsed and Refractory Multiple Myeloma Patients
A Phase 2 study testing dasatinib, melphalan and prednisone in people with Myeloma, run by Fondazione EMN Italy Onlus at 1 site in Italy.
Trial summary
Clinically demonstrated efficacy of Melphalan and Prednisone in MM subjects as well as the confirmed inhibitory effect of dasatinib on several tyrosine kinase receptors and pathways implicated in the pathophysiology of MM. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Myeloma
- What is being tested?
- dasatinib, melphalan and prednisone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2008to May 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years and ≤75 year
- Karnofsky performance status ≥ 60%
- Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
- 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
- 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.
- Patient was previously diagnosed with symptomatic MM based on standard criteria, and has measurable disease, defined as follows:
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- 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).
- 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).
- Patient has a life-expectancy > 3 months
- 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.
- Patient has the ability to take oral medication (dasatinib must be swallowed whole)
- Concomitant Medications:
- Patient agrees that IV bisphophonates will be withheld for the first 8 weeks of Dasatinib therapy due to risk of hypocalcemia.
- 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).
Who cannot join
- Patients with > 2 previous treatment regimens.
- Multiple myeloma treatment (ie, chemotherapy, biological, immunotherapy or investigational agent [therapeutic or diagnostic]) administered within 21 days prior to treatment initiation.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females.
- 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.
- Use of any other concomitant standard/experimental anti-myeloma drug or therapy
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- Concurrent anticoagulation treatment or medications that directly or durably inhibit platelet function.
- 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.
- Concurrent medical condition which may increase the risk of toxicity, including:
- Pleural or pericardial effusion of any grade
- Clinically significant cardiac disease (NYHA classification III and IV); any of the following should be considered for exclusion:
- Uncontrolled angina, congestive heart failure or MI within (6 months)
- Diagnosed congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
- Subjects with hypokalemia or hypomagnesemia, if it cannot be corrected prior to dasatinib administration.
- History of significant bleeding disorder unrelated to cancer, including:
- Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
- Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
- Ongoing or recent (< 3 months) significant gastrointestinal bleeding.
- Concomitant Medications, any of the following should be considered for exclusion:
- 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.
- 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.
- 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.
- Women who:
- 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 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.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
- Patient that assume anti-arrhythmic drugs or other medicinal products which led to QT prolongation and cumulative high dose anthracycline.
- Patient has active infectious hepatitis type B or C or HIV.
- Patient has known intolerance to lactose
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
Clinically demonstrated efficacy of Melphalan and Prednisone in MM subjects as well as the confirmed inhibitory effect of dasatinib on several tyrosine kinase receptors and pathways implicated in the pathophysiology of MM. Additionally, as a SRC inhibitor, dasatinib plays an important role on bone metabolism through inhibition of osteoclast-mediated bone resorption in vitro. Dasatinib could, thus, be beneficial on bone density of patients on study, through blockage of osteolysis and control of bone lesions.
Read the detailed description
Primary Objective: To determine whether the combination of dasatinib with melphalan and prednisone provides therapeutic benefits and is safe in patients with relapsed/refractory Multiple Myeloma.
Study design, dose and mode of administration, and duration of treatment: Multicenter, open-label, single arm, two-stage, Phase II study of dasatinib in combination with melphalan and prednisone (D-MP) in advanced, refractory MM patients. The three drugs will be concurrently administered through 6 cycles; each cycle will be 28 days long (1 cycle = 4 weeks), for a total of 24 weeks of treatment. The treatment schedule will be the following:
- Melphalan 0,18 mg/Kg/day from day 1 to day 4 for 6 cycles;
- Prednisone 1,5 mg/Kg/day from day 1 to day 4 for 6 cycles;
- Dasatinib 100 mg QD continuously (from day 1 to day 28). After the 6 cycles of D-MP treatment, Dasatinib will be continuously administered alone as maintenance, until occurrence of progressive disease, unacceptable toxicity or informed consent withdrawal.
This is a two-stage Phase II trial according to Simon with a bivariate endpoint design, by which treatment efficacy and safety are jointly evaluated. This design allows the trial to be early stopped after the first stage if the number of observed partial responses (PR) is inadequate and the number of observed toxicities is too high. In the first stage of the protocol 17 patients are required.
- Conditions
- Myeloma
- Being tested
- dasatinib, melphalan, prednisone
- Keywords
- relapsed/refractory myeloma patients, Progression free survival, Overall survival, dasatinib
- Medical subject headings
- Neoplasms, Plasma Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dasatinibDrug
100 mg QD continuously (from day 1 to day 28)
melphalanDrug
0,18 mg/Kg/day from day 1 to day 4 for 6 cycles
prednisoneDrug
1,5 mg/Kg/day from day 1 to day 4 for 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| D-MP | Experimental | Not described Receives: Drug: dasatinib; Drug: melphalan; Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Partial response rate is a primary study endpoint.
Evaluation of tumor status will be conducted at screening and anti-tumor treatment efficacy will be assessed at every cycle according to the International Uniform Criteria for Response in MM.
Safety and tolerability are a co-primary endpoint: incidence of grade 3-4 toxicities will support the decision to move to stage 2, together with PR rate once all the patients accrued to the first stage are evaluable.
Measured: 4 years
Secondary outcomes (1)
Secondary objectives are progression-free survival and overall survival
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2010 (estimated)
- Study startFeb 2008
- Primary completionMay 2011
- Study completionMay 2011
Why it stopped: difficulty in enrolling patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione EMN Italy Onlus
- Sponsor type
- University, hospital or other
- Investigators
- Mario Boccadoro, MD, Principal investigator, Divisione Universitaria di Ematologia Ospedale Molinette di Torino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01116128
- Sponsor's protocol ID
- CA180-210
- Acronym
- D-MP
- Status last verified
- Jun 2011
- First submitted
- 17 Mar 2010
- Last updated
- 14 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01116128
- Acronym / sponsor ID
- D-MP / CA180-210
- Conditions
- Myeloma
- Keywords
- relapsed/refractory myeloma patients, Progression free survival, Overall survival, dasatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: difficulty in enrolling patients
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Fondazione EMN Italy OnlusUniversity, hospital or other
- Study start
- Feb 2008
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 4 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clinically demonstrated efficacy of Melphalan and Prednisone in MM subjects as well as the confirmed inhibitory effect of dasatinib on several tyrosine kinase receptors and pathways implicated in the pathophysiology of MM. Additionally, as a SRC inhibitor, dasatinib plays an important role on bone metabolism through inhibition of osteoclast-mediated bone resorption in vitro. Dasatinib could, thus, be beneficial on bone density of patients on study, through blockage of osteolysis and control of bone lesions.
Detailed description
Primary Objective: To determine whether the combination of dasatinib with melphalan and prednisone provides therapeutic benefits and is safe in patients with relapsed/refractory Multiple Myeloma.
Study design, dose and mode of administration, and duration of treatment: Multicenter, open-label, single arm, two-stage, Phase II study of dasatinib in combination with melphalan and prednisone (D-MP) in advanced, refractory MM patients. The three drugs will be concurrently administered through 6 cycles; each cycle will be 28 days long (1 cycle = 4 weeks), for a total of 24 weeks of treatment. The treatment schedule will be the following:
- Melphalan 0,18 mg/Kg/day from day 1 to day 4 for 6 cycles;
- Prednisone 1,5 mg/Kg/day from day 1 to day 4 for 6 cycles;
- Dasatinib 100 mg QD continuously (from day 1 to day 28). After the 6 cycles of D-MP treatment, Dasatinib will be continuously administered alone as maintenance, until occurrence of progressive disease, unacceptable toxicity or informed consent withdrawal.
This is a two-stage Phase II trial according to Simon with a bivariate endpoint design, by which treatment efficacy and safety are jointly evaluated. This design allows the trial to be early stopped after the first stage if the number of observed partial responses (PR) is inadequate and the number of observed toxicities is too high. In the first stage of the protocol 17 patients are required.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| D-MP | Experimental | Drug: dasatinib, Drug: melphalan, Drug: prednisone |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age ≥ 18 years and ≤75 year
- Karnofsky performance status ≥ 60%
- Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
- 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.
- 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.
Key exclusion criteria (37 listed)
- Patients with > 2 previous treatment regimens.
- Multiple myeloma treatment (ie, chemotherapy, biological, immunotherapy or investigational agent [therapeutic or diagnostic]) administered within 21 days prior to treatment initiation.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dasatinib100 mg QD continuously (from day 1 to day 28) | Drug | D-MP |
| melphalan0,18 mg/Kg/day from day 1 to day 4 for 6 cycles | Drug | D-MP |
| prednisone1,5 mg/Kg/day from day 1 to day 4 for 6 cycles | Drug | D-MP |
Primary outcome
Partial response rate is a primary study endpoint.
Time frame: 4 years
Evaluation of tumor status will be conducted at screening and anti-tumor treatment efficacy will be assessed at every cycle according to the International Uniform Criteria for Response in MM. Safety and tolerability are a co-primary endpoint: incidence of grade 3-4 toxicities will support the decision to move to stage 2, together with PR rate once all the patients accrued to the first stage are evaluable.
1 secondary outcome
Secondary objectives are progression-free survival and overall survival
Time frame: 4 years
Results and safety
The study was stopped early (reason given: difficulty in enrolling patients). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Boccadoro, MD principal investigator
Divisione Universitaria di Ematologia Ospedale Molinette di Torino
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing dasatinib, melphalan and prednisone in people with Myeloma, run by Fondazione EMN Italy Onlus at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: difficulty in enrolling patients). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Partial response rate is a primary study endpoint. (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2011.