iCare 2: Personalized Genomic Mutation Informed Treatment of Patients With Myelodysplastic Syndromes
Overview
- Phase
- Not Applicable
- Intervention
- FDA-approved drug or combination of drugs
- Conditions
- Myelodysplastic Syndromes
- Sponsor
- University of Florida
- Locations
- 1
- Primary Endpoint
- Difference in overall response, as measured by International Working Group (IWG) 2006 criteria for response in MDS
- Status
- Withdrawn
- Last Updated
- 6 years ago
Overview
Brief Summary
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).
Detailed Description
It is hypothesized that personalized treatment informed by computational biology simulation technology will improve treatment outcomes for patients with relapsed or refractory MDS.
Investigators
Eligibility Criteria
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:
- •Must agree to use physician-approved contraceptive methods (e.g., abstinence, intrauterine device, oral contraceptive, double barrier device) throughout the study and for 3 months following the last dose of study treatment; and
- •Must have a negative serum or urine pregnancy test within 7 days prior to beginning treatment on this trial
- •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
- •Must not have acute myeloid leukemia (AML), as defined by WHO 2008
- •Pregnant and nursing subjects are excluded because the effects of study treatments on a fetus or nursing child are unknown
- •Must not have had treatment with any anti-cancer therapy (investigational or standard) within the previous 21 days prior to the first dose of study drug or less than full recovery (no worse than CTCAE v4.0 grade 1) from the clinically significant toxic effects of that treatment.
Arms & Interventions
Computational Biology-Informed Treatment
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.
Intervention: FDA-approved drug or combination of drugs
Computational Biology-Informed Treatment
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.
Intervention: Computational biology simulations software
Standard of Care Treatment
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.
Intervention: FLAG induction
Standard of Care Treatment
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.
Intervention: 7 + 3 induction
Standard of Care Treatment
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.
Intervention: Low-dose cytarabine
Standard of Care Treatment
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.
Intervention: Supportive care alone
Outcomes
Primary Outcomes
Difference in overall response, as measured by International Working Group (IWG) 2006 criteria for response in MDS
Time Frame: 4 months
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
Secondary Outcomes
- 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 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 safety and feasibility, as measured by CTCAE v4.0 criteria(5 months)
- Difference in time to death between patients treated with computational biology-informed therapy and those treated with standard of care regimens(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 blood transfusion rate between patients treated with computational biology-informed therapy and those treated with standard of care regimens(7 months)