Myelodysplastic SyndromesNCT00624585
Study of Oral Dasatinib in Subjects With Myelodysplastic Syndrome (MDS) and Excess Marrow Blasts
A study testing Dasatinib in people with Myelodysplastic Syndromes, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The main purpose of this study is to learn how patients with myelodysplastic syndrome (MDS) respond to the study drug dasatinib. The study drug, dasatinib, has been approved by the U.S. Food and Drug Administration (FDA) for treatment of leukemia, but has not been approved for the treatment of other kinds of cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- Dasatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to May 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented diagnosis of MDS or Myeloproliferative Disorders (MPS/MPD) with blast percentage > 10% in bone marrow, MDS/AML with <30% blasts:
- MDS [all World Health Organization (WHO) types] with blast percentage > 10% in bone marrow
- Chronic myelomonocytic leukemia (CMML) with blast percentage > 10% in bone marrow
- Myelodysplastic / Myeloproliferative (MDS/MPD) syndromes with blast percentage > 10% in bone marrow
- Acute myeloid leukemia with Multilineage Dysplasia (MDS/AML) with <30% blasts and declined standard induction chemotherapy or deemed unfit for standard induction chemotherapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
Show all 17Show fewer
- Previous therapy with Azacitidine or Decitabine with last dose at least 2 months prior to first dose of dasatinib okay. Must be at least 4 weeks out from any previous investigational therapy.
- Adequate Organ Function
- Total bilirubin < 2.0 times institutional Upper Limit of Normal (ULN)
- Hepatic enzymes (AST, ALT) ≤ 2.5 times institutional ULN
- Serum Na, K+, Mg2+, Phosphate and Ca2+≥ Lower Limit of Normal (LLN) [low electrolyte levels must be repleted to all for entry]
- Serum Creatinine < 1.5 times ULN
- Prothrombin time (PT), partial thromboplastin time (PTT) Grade 0-1
- Able to take oral medication (Dasatinib must be swallowed whole. Tablets can be dissolved in juice and then put down an NG/G tube or drank as a solution)
- Women of childbearing potential (WOCBP) must have Negative serum or urine pregnancy test within 72 hours prior to start of study drug
- Persons of reproductive potential must agree to use adequate birth control throughout treatment and at least 4 weeks after study drug is stopped
- Signed written informed consent
Who cannot join
- White blood count (WBC) >50,000 off hydroxyurea for >72 hours
- Malignancy [other than the one treated in this study] requiring radiotherapy or systemic treatment within past 3 years
- Chemotherapy or any agent with activity in MDS or AML concurrent with the study.
- Chemotherapy for MDS or AML prior to enrollment not allowed other than Azacitidine or Decitabine >2 months prior to first dose
- Concurrent medical condition which may increase the risk of toxicity, including:
- Pleural or pericardial effusion
Show all 28Show fewer
- Serious medical condition, unstable medical co-morbidity, psychiatric illness that will prevent subject from signing informed consent form or place them at unacceptable risk if they participate
- Cardiac Symptoms, including:
- Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within 6 months
- Diagnosed congenital long QT syndrome
- 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)
- Hypokalemia or hypomagnesemia if cannot be corrected
- History of significant bleeding disorder unrelated to cancer, including:
- Congenital bleeding disorders
- Acquired bleeding disorder within 1 year
- Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding
- Concomitant Medications, consider the following prohibitions:
- Drugs generally accepted to have risk of causing Torsades de Pointes(Must discontinue drug 7 days prior to starting dasatinib)
- Concomitant use of H2 blockers or proton pump inhibitors with dasatinib not recommended. Use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy.
- On-going requirement for treatment with platelet function inhibitor or anti-coagulation.
- Must discontinue St. Johns Wort while receiving dasatinib therapy
- Must agree that intravenous (IV) bisphosphonates be withheld for first 8 weeks of Dasatinib therapy due to risk of hypocalcemia.
- May not be receiving any prohibited CYP3A4 inhibitors
- Women:
- Positive pregnancy test at baseline
- Pregnant or breastfeeding
- Prisoners or patients who are compulsorily detained for treatment of either psychiatric or physical (e.g., infectious) illness
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Pilot Study of Oral Dasatinib in Subjects With MDS and Excess Marrow Blasts
The main purpose of this study is to learn how patients with myelodysplastic syndrome (MDS) respond to the study drug dasatinib. The study drug, dasatinib, has been approved by the U.S. Food and Drug Administration (FDA) for treatment of leukemia, but has not been approved for the treatment of other kinds of cancer. The use of dasatinib in this study is considered experimental.
Read the detailed description
Study Core Period:
The first 16 weeks after the initial dose of dasatinib is called the Study Core Period. Patients who are eligible and chose to participate in this study should expect to take 100 mg of dasatinib daily for 8 weeks. If the study doctor believes that they have not achieved a partial response after 8 weeks of treatment, the dose may be increased to 150 mg per day. The study doctor may lower the dosage of dasatinib if the 100 mg treatment is too strong. If the lower dose of dasatinib is still too strong, the study doctor may decide to take the patient off of the study. The patient will continue to receive supportive care as needed during the duration of the trial as well as after completion of the trial.
During the Study Core Period, participants will have a study visit every 4 weeks. Complete Blood Counts (CBCs) will be obtained every 2 weeks for study purposes and disease monitoring. Bone marrow aspiration and biopsy will be obtained at screening, and at 8 weeks and 16 weeks of treatment for response assessment. Additional bone marrow aspirations and biopsies may be obtained at any other time, to evaluate the disease process, at the doctor's judgment. A bone marrow aspirate and biopsy must be done at the time of study discontinuation.
Study Extension Period:
The time after the first 16 weeks of treatment is called the study extension period. If the patient is responding to the treatment, does not experience disease progression or any severe adverse events, the patient may continue dasatinib treatment for up to 48 weeks. If patients continue after 48 weeks, they will be asked to enroll in a separate extension study for future follow up.
During the Study Extension Period, participants will have a study visit every 4 weeks. Complete Blood Counts (CBCs) will be obtained every 2 or 4 weeks for study purposes and disease monitoring. Bone marrow aspiration and biopsy will be obtained every 16 weeks. A bone marrow aspirate and biopsy must be done at the time of study discontinuation.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- Dasatinib
- Keywords
- MDS, MDS/MPD, MDS/AML, CMML, Excess Marrow Blasts
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called SPRYCEL®
DOSE ESCALATION OF DASATINIB AFTER 8 WEEKS IF ELIGIBLE
- Dose Level and Dose of dasatinib:
- Starting dose (1-8 weeks)= 100 mg orally (po) daily
- +1 (<8 weeks if no PR and well tolerated) = 150 mg po daily
DOSE MODIFICATION OF DASATINIB
- Dose Level and Dose of dasatinib:
- Starting dose = 100 mg po daily
- -1 = 70 mg po daily
- -2 = 50 mg po daily
OR
- Dose Level and Dose of dasatinib:
- Starting dose = 150 mg po daily
- -1 = 120 mg po daily
- -2 = 90 mg po daily
- -3 = 50 mg po daily
| Study group | Role | What they receive |
|---|---|---|
| Dasatinib Dose Escalation | Experimental | Patients will be started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose is well tolerated and patient has not achieved a partial response, the dose may be increased to 150 mg per day. All patients will be followed per protocol for a total core period of 16 weeks from the first dose. Responding patients will continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up. Receives: Drug: Dasatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Marrow Complete Remission (CR)
Complete remission (modified IWG); IWG = International MDS Working Group.
Bone Marrow Response must last ≥4 weeks. Bone marrow evaluation: Bone marrow showing ≤5% myeloblasts with normal maturation of all cell lines.
Measured: 1 Year 4 Months
Secondary outcomes (3)
Number of Participants With Hematologic Improvement
Hematologic improvement in platelets, red blood cell (RBC), neutrophils according to modified IWG Criteria; Cytogenetic response (modified IWG); Change in percentage of blasts in bone marrow and peripheral blood; Src-Tyr416 phosphorylation in medullary myeloblasts. Hematologic improvements must last ≥ 8 weeks.
Measured: 1 Year 4 Months
Number of Participants With Partial Remission (PR)
Partial remission (PR) (modified IWG); IWG = International MDS Working Group. All of the CR criteria (if abnormal prior to treatment), except: Bone marrow evaluation: Blasts decreased by ≥ 50% over pretreatment but still >5%. Cellularity and morphology are not relevant.
Measured: 1 Year 4 Months
Number of Participants With Stable Disease (SD)
Measured: 1 Year 4 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Alan List, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00624585
- Sponsor's protocol ID
- MCC-15276
- Other IDs
- CA180-106
- Status last verified
- May 2012
- First submitted
- 15 Feb 2008
- Last updated
- 16 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Oral Dasatinib in Subjects With MDS and Excess Marrow Blasts
- ClinicalTrials.gov ID
- NCT00624585
- Acronym / sponsor ID
- MCC-15276
- Conditions
- Myelodysplastic Syndromes
- Keywords
- MDS, MDS/MPD, MDS/AML, CMML, Excess Marrow Blasts
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Feb 2008
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 27 Feb 2008 (estimated)
- Results
- Posted 25 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to learn how patients with myelodysplastic syndrome (MDS) respond to the study drug dasatinib. The study drug, dasatinib, has been approved by the U.S. Food and Drug Administration (FDA) for treatment of leukemia, but has not been approved for the treatment of other kinds of cancer. The use of dasatinib in this study is considered experimental.
Detailed description
Study Core Period:
The first 16 weeks after the initial dose of dasatinib is called the Study Core Period. Patients who are eligible and chose to participate in this study should expect to take 100 mg of dasatinib daily for 8 weeks. If the study doctor believes that they have not achieved a partial response after 8 weeks of treatment, the dose may be increased to 150 mg per day. The study doctor may lower the dosage of dasatinib if the 100 mg treatment is too strong. If the lower dose of dasatinib is still too strong, the study doctor may decide to take the patient off of the study. The patient will continue to receive supportive care as needed during the duration of the trial as well as after completion of the trial.
During the Study Core Period, participants will have a study visit every 4 weeks. Complete Blood Counts (CBCs) will be obtained every 2 weeks for study purposes and disease monitoring. Bone marrow aspiration and biopsy will be obtained at screening, and at 8 weeks and 16 weeks of treatment for response assessment. Additional bone marrow aspirations and biopsies may be obtained at any other time, to evaluate the disease process, at the doctor's judgment. A bone marrow aspirate and biopsy must be done at the time of study discontinuation.
Study Extension Period:
The time after the first 16 weeks of treatment is called the study extension period. If the patient is responding to the treatment, does not experience disease progression or any severe adverse events, the patient may continue dasatinib treatment for up to 48 weeks. If patients continue after 48 weeks, they will be asked to enroll in a separate extension study for future follow up.
During the Study Extension Period, participants will have a study visit every 4 weeks. Complete Blood Counts (CBCs) will be obtained every 2 or 4 weeks for study purposes and disease monitoring. Bone marrow aspiration and biopsy will be obtained every 16 weeks. A bone marrow aspirate and biopsy must be done at the time of study discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dasatinib Dose Escalation | Experimental | Drug: DasatinibPatients will be started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose is well tolerated and patient has not achieved a partial response, the dose may be increased to 150 mg per day. All patients will be followed per protocol for a total core period of 16 weeks from the first dose. Responding patients will continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Documented diagnosis of MDS or Myeloproliferative Disorders (MPS/MPD) with blast percentage > 10% in bone marrow, MDS/AML with <30% blasts:
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- Previous therapy with Azacitidine or Decitabine with last dose at least 2 months prior to first dose of dasatinib okay. Must be at least 4 weeks out from any previous investigational therapy.
- Adequate Organ Function
- Able to take oral medication (Dasatinib must be swallowed whole. Tablets can be dissolved in juice and then put down an NG/G tube or drank as a solution)
Key exclusion criteria (28 listed)
- White blood count (WBC) >50,000 off hydroxyurea for >72 hours
- Malignancy [other than the one treated in this study] requiring radiotherapy or systemic treatment within past 3 years
- Chemotherapy or any agent with activity in MDS or AML concurrent with the study.
- Chemotherapy for MDS or AML prior to enrollment not allowed other than Azacitidine or Decitabine >2 months prior to first dose
- Concurrent medical condition which may increase the risk of toxicity, including:
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 |
|---|---|---|
| DasatinibAlso: SPRYCEL®DOSE ESCALATION OF DASATINIB AFTER 8 WEEKS IF ELIGIBLE * Dose Level and Dose of dasatinib: 1. Starting dose (1-8 weeks)= 100 mg orally (po) daily 2. +1 (<8 weeks if no PR and well tolerated) = 150 mg po daily DOSE MODIFICATION OF DASATINIB * Dose Level and Dose of dasatinib: 1. Starting dose = 100 mg po daily 2. -1 = 70 mg po daily 3. -2 = 50 mg po daily OR * Dose Level and Dose of dasatinib: 1. Starting dose = 150 mg po daily 2. -1 = 120 mg po daily 3. -2 = 90 mg po daily 4. -3 = 50 mg po daily | Drug | Dasatinib Dose Escalation |
Primary outcome
Number of Participants With Marrow Complete Remission (CR)
Time frame: 1 Year 4 Months
Complete remission (modified IWG); IWG = International MDS Working Group. Bone Marrow Response must last ≥4 weeks. Bone marrow evaluation: Bone marrow showing ≤5% myeloblasts with normal maturation of all cell lines.
3 secondary outcomes
Number of Participants With Hematologic Improvement
Time frame: 1 Year 4 Months
Number of Participants With Partial Remission (PR)
Time frame: 1 Year 4 Months
Number of Participants With Stable Disease (SD)
Time frame: 1 Year 4 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Myelodysplastic Syndromes
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Alan List, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dasatinib in people with Myelodysplastic Syndromes, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
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 17 inclusion and 28 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: finished, as of the sponsor's last update on 16 Dec 2013. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Marrow Complete Remission (CR) (time frame: 1 Year 4 Months). 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 16 Dec 2013.