SB1518 for Patients With Myelodysplastic Syndrome (MDS)
Study Details
Study Description
Brief Summary
The goal of this clinical research study is to learn if SB1518 can help to control myelodysplastic syndrome. The safety of the drug will also be studied.
SB1518 is designed to block JAK2 and FLT3. SB1518 may have anti-tumor activity in certain leukemias, myelofibrosis, and lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take SB1518 by mouth 1 time every day. You can take it with or without food, and it should be taken at the same time every day.
You will receive your monthly supply of SB1518 during your clinic visit. The capsules should not be opened or crushed. Do not touch the powder in the capsules. If you do, wash effected areas thoroughly with water.
Each study cycle is 28 days.
Study Visits:
At every study visit, you will be asked about any drugs you may be taking, and any side effects you have had.
One (1) time a week during Cycle 1, blood (about 2 tablespoons) will be drawn for routine tests.
On Day 1 of Cycles 2 and beyond, blood (about 2 tablespoons) will be collected for routine tests.
On Day 28 of each cycle, you will have a bone marrow aspirate and/or biopsy to check the status of the disease. If the screening bone marrow test showed unusual genetic test results, these samples will be used for cytogenetic testing. If you have a response to therapy, you will have a bone marrow aspirate and/or biopsy every 3 cycles, if your doctor thinks it needed.
Length of Study:
You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, you are able to undergo allogeneic bone marrow transplantation, or if you are unable to follow study directions.
Your participation on the study will be over once you have completed the end-of-treatment visit.
End-of-Treatment Visit:
At 30 days after your last dose of study drug, you will have an end-of-treatment visit.
-
You will be asked about any drugs you may be taking, and any side effects you have had.
-
Blood (about 2 tablespoons) will be drawn for routine tests.
-
You will have a bone marrow aspirate and/or biopsy to check the status of the disease, if your doctor thinks it is needed.
This is an investigational study. SB1518 is not FDA approved or commercially available. It is currently being used for research purposes only.
Up to 40 participants will take part in this study. All will be enrolled at MD Anderson.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SB1518 400 mg orally a day for 28 day cycle. |
Drug: SB1518
400 mg taken orally, once daily without regard of food, 28 day cycle.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Overall Response [28 days to one year]
Overall response based on hematologic improvement defined by International Working Group (IWG) response criteria in myelodysplasia. Complete remission (CR): Bone marrow of 5% myeloblasts with normal maturation of all cell lines, noted persistent dysplasia; Partial Remission: CR criteria if abnormal before treatment except Bone marrow blasts decreased by 50% over pretreatment but still > 5%; Marrow CR: Bone marrow 5% myeloblasts and decrease by 50% over pretreatment. Bone marrow aspirate pre-therapy (Day 0) and on Day 28 of first cycle then every 3 cycles. Responses must last at least 4 weeks.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with MDS by the IPSS classification including low, int-1, int-2, and high risk are eligible. Patients should have received at least one line of prior therapy including growth factors, lenalidomide, or hypomethylating agents.
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Signed informed consent.
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Age >/= 18 years old.
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Patients must have the following non-hematologic values: Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) </= 2.5 x Upper Limit of Normal (ULN) if both are available or </= 5.0 x ULN if hepatic involvement is present as determined by the investigator; Serum bilirubin </=2 x ULN; Serum creatinine </= 2 x ULN or 24-hour creatinine clearance >/= 50 ml/min
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Patients, if sexually active, must agree to use appropriate forms birth control.
Exclusion Criteria:
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Uncontrolled intercurrent illness, including but not limited to ongoing active infection or psychiatric illness or social situations that the treating physician judges would limit compliance with study requirements. Patients receiving antibiotics for infections that are under control may be included in the study.
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History of myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within 6 months prior to study enrollment;
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New York Heart Association Class III or IV congestive heart failure;
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Ongoing cardiac dysrhythmias of Grade >/= 2, atrial fibrillation of any grade, QTc prolongation > 470 ms or other factors that increase the risk of QT prolongation (e.g., heart failure; hypokalemia, defined as serum potassium < 3.0 mEq/L; family history of long QT interval syndrome);
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Required use of a concomitant medication known to prolong the QT interval significantly.
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Known HIV seropositivity;
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Known active hepatitis A, B, or C;
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Women who are pregnant or lactating.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UT MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- S*BIO
Investigators
- Principal Investigator: Guillermo Garcia-Manero, MD, UT MD Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2011-0427
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: December 22, 2011 to January 24, 2012. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail | Four participants of the eight enrolled failed to meet the screening criteria and were not treated on the study. The study was closed to new patient entry 2 months after activation due to sponsor/collaborator issues; the only patient remaining was taken off study at that time. |
| Arm/Group Title | SB1518 |
|---|---|
| Arm/Group Description | 400 mg orally a day for 28 day cycle. |
| Period Title: Overall Study | |
| STARTED | 4 |
| COMPLETED | 0 |
| NOT COMPLETED | 4 |
Baseline Characteristics
| Arm/Group Title | SB1518 |
|---|---|
| Arm/Group Description | 400 mg orally a day for 28 day cycle. |
| Overall Participants | 4 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
69
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
25%
|
| Male |
3
75%
|
| Region of Enrollment (participants) [Number] | |
| United States |
4
100%
|
Outcome Measures
| Title | Number of Participants With Overall Response |
|---|---|
| Description | Overall response based on hematologic improvement defined by International Working Group (IWG) response criteria in myelodysplasia. Complete remission (CR): Bone marrow of 5% myeloblasts with normal maturation of all cell lines, noted persistent dysplasia; Partial Remission: CR criteria if abnormal before treatment except Bone marrow blasts decreased by 50% over pretreatment but still > 5%; Marrow CR: Bone marrow 5% myeloblasts and decrease by 50% over pretreatment. Bone marrow aspirate pre-therapy (Day 0) and on Day 28 of first cycle then every 3 cycles. Responses must last at least 4 weeks. |
| Time Frame | 28 days to one year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study was halted prior to completion of treatment and assessment for any participant(s). |
| Arm/Group Title | SB1518 |
|---|---|
| Arm/Group Description | 400 mg orally a day for 28 day cycle. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | Adverse event data collected during 28 day drug cycles to thirty days following the last dose of study drug. In the absence of treatment delays due to adverse events, treatment may continue indefinitely. Study period December 2011 to January 2012. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | SB1518 | |
| Arm/Group Description | 400 mg orally a day for 28 day cycle. | |
All Cause Mortality |
||
| SB1518 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| SB1518 | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| SB1518 | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | |
| Gastrointestinal disorders | ||
| Gastrointestinal (GI) Other | 1/4 (25%) | 1 |
| Diarrhea | 2/4 (50%) | 2 |
| Heartburn | 1/4 (25%) | 1 |
| General disorders | ||
| Abdominal pain | 1/4 (25%) | 1 |
| Nausea | 2/4 (50%) | 2 |
| Fatigue | 2/4 (50%) | 2 |
| Pain Other | 1/4 (25%) | 1 |
| Vomiting | 1/4 (25%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Sweating | 1/4 (25%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Guillermo Garcia-Manero, MD / Professor, Leukemia |
|---|---|
| Organization | University of Texas (UT) MD Anderson Cancer Center |
| Phone | 1-877-MDA-6789 |
| CR_Study_Registration@mdanderson.org |
- 2011-0427