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

NCT01116128 | Terminated Phase 2 DMC

• 1 other identifier: CA180-210
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Myeloma

Keywords

relapsed/refractory myeloma patients; Progression free survival; Overall survival; dasatinib

Outcome Measures

Primary Outcomes (1)

• 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.

  4 years

Secondary Outcomes (1)

• Secondary objectives are progression-free survival and overall survival

  4 years

Study Arms (1)

D-MP

EXPERIMENTAL

Drug: dasatinib; Drug: melphalan; Drug: prednisone

Interventions

dasatinib DRUG

100 mg QD continuously (from day 1 to day 28)

D-MP

melphalan DRUG

0,18 mg/Kg/day from day 1 to day 4 for 6 cycles

D-MP

prednisone DRUG

1,5 mg/Kg/day from day 1 to day 4 for 6 cycles

D-MP

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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:
• 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:

You may not qualify if:

• 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
• 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
• 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.

Sponsors & Collaborators

• Fondazione EMN Italy Onlus: lead

Study Sites (1)

Mario Boccadoro

Torino, 10126, Italy

Location

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Recurrence

Interventions

Dasatinib; Melphalan; Prednisone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Mario Boccadoro, MD

  Divisione Universitaria di Ematologia Ospedale Molinette di Torino

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 17, 2010
• First Posted: May 4, 2010
• Study Start: February 1, 2008
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 14, 2011

Record last verified: 2011-06

Locations

IT (1)