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| ID | Type | Description | Link |
|---|---|---|---|
| OCR17918 | Other Identifier | UF OnCore | |
| IRB201702867 | Other Identifier | University of Florida |
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administratively withdrawn
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| Name | Class |
|---|---|
| Gateway for Cancer Research | OTHER |
| Cellworks Group Inc. | INDUSTRY |
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This open-label, randomized, parallel group phase II study will investigate the efficacy of computational biology-informed treatment vs. standard of care treatment for patients with relapsed or refractory myelodysplastic syndromes (MDS).
It is hypothesized that personalized treatment informed by computational biology simulation technology will improve treatment outcomes for patients with relapsed or refractory MDS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Computational Biology-Informed Treatment | Experimental | Patients randomized to this arm will receive an FDA-approved drug or combination of drugs predicted to have a therapeutic effect based on their individual MDS disease genetic profile by a computational biology simulation software program. The specific drug or combination of drugs that a patient on this arm will receive will be decided jointly by a molecular oncology board comprised of physicians, pharmacists, and nurse coordinators and the treating physician. Patients will receive a minimum of 2 months and a maximum of 4 months of treatment with the selected drug or combination of drugs. |
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| Standard of Care Treatment | Active Comparator | Patients randomized to this arm will receive either one of three standard of care treatment regimens of the treating physician's choice (low-dose cytarabine, 7 + 3 induction, or FLAG induction) or supportive care alone. Patients will receive a minimum of 2 months and a maximum of 4 months of the selected treatment regimen or of supportive care alone. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FDA-approved drug or combination of drugs | Drug | Patients assigned to this arm will receive an FDA-approved drug or combination of drugs. Dosing and treatment schedule will follow the package insert for the selected drug(s). |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in overall response, as measured by International Working Group (IWG) 2006 criteria for response in MDS | Difference in overall response (number of patients who achieve complete response, partial response, stable disease, or hematologic improvement per IWG 2006 criteria) between patients treated with computational biology-informed therapy vs. those treated with standard of care regimens | 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in safety and feasibility, as measured by CTCAE v4.0 criteria | Difference in safety and feasibility, as measured by CTCAE v4.0 criteria, between patients treated with computational biology-informed treatment and those who receive a standard of care regimen | 5 months |
| Difference in time to death between patients treated with computational biology-informed therapy and those treated with standard of care regimens |
| Measure | Description | Time Frame |
|---|---|---|
| Differences in mutant allele frequencies between patients treated with computational biology-informed therapy and those treated with standard of care regimens | 4 months | |
| Laboratory correlations between computational model and actual intracellular pathway activation status |
Inclusion Criteria:
Provide written informed consent
Must be at least 18 years of age
Diagnosis of MDS, as defined by World Health Organization (WHO) 2008, that has relapsed after any duration of time from last best response or is refractory to induction therapy (defined as 4 cycles of treatment with a hypomethylating agent, 2 cycles of lenalidomide, 1 cycle of low intensity chemotherapy, or 1 cycle of high intensity chemotherapy)
ECOG performance status of 0-2
Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) may participate, provided they meet the following conditions:
Males with female partners of child-bearing potential must agree to use physician approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 6 months following the last dose of study treatment.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Cogle, MD | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida | Gainesville | Florida | 32608 | United States |
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| FLAG induction | Drug | Patients will receive 30 mg/m2 per day intravenously of fludarabine for 5 days and 2000 mg/m2 per day intravenously of cytarabine for 5 days. 5 mg/kg per day of granulocyte colony stimulating factor (G-CSF) may be given subcutaneously beginning on Day 1 of each treatment until absolute granulocyte count > 500/ microliter for 3 days. |
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| 7 + 3 induction | Drug | Patients will receive 100-200 mg/m2 per day intravenously of cytarabine for 7 days, plus either 45-60 mg/m2 per day intravenously of daunorubicin or 9-12 mg/m2 per day intravenously of idarubicin for 3 days. |
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| Low-dose cytarabine | Drug | Patients will receive 20 mg/m2 per day subcutaneously of cytarabine for 10 days every 28 days. |
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| Supportive care alone | Other | Patients will receive one or more of the following: blood product transfusions, antibiotics, granulocyte colony-stimulating factor (G-CSF), erythropoietic stimulating factors, and iron chelation. |
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| Computational biology simulations software | Device | Genetic testing results for each patient randomized to this arm will be used by a computational biology simulations software program to generate a personalized map of dysregulated metabolic pathways contributing to the patient's disease. This map will then be used to digitally screen for potentially therapeutic FDA-approved drugs or drug combinations to target the dysregulated metabolic pathways. |
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| 3 years |
| Difference in time to progression to acute myeloid leukemia (AML), as measured by IWG 2006 criteria for response in MDS, between patients treated with computational biology-informed therapy and those treated with standard of care regimens | 4 months |
| Difference in time to disease relapse, as measured by IWG 2006 criteria for response in MDS, between patients treated with computational biology-informed therapy and those treated with standard of care regimens | 4 months |
| Difference in time to best response, as measured by IWG 2006 criteria for response in MDS, between patients treated with computational biology-informed therapy and those treated with standard of care regimens | 4 months |
| Difference in change in myeloblast percentage between patients treated with computational biology-informed therapy and those treated with standard of care regimens | 4 months |
| Difference in blood transfusion rate between patients treated with computational biology-informed therapy and those treated with standard of care regimens | 7 months |
| 4 months |
| Clinical correlations between pharmacogenotypes and drug efficacy (as measured by IWG 2006 criteria for response in MDS) | 4 months |
| Clinical correlations between pharmacogenotypes and drug-related adverse events (as measured by CTCAE v4.0 criteria) | 5 months |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D003561 | Cytarabine |
| D010166 | Palliative Care |
| ID | Term |
|---|---|
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D005791 | Patient Care |
| D013812 | Therapeutics |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
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