iCare 2: Personalized Genomic Mutation Informed Treatment of Patients With Myelodysplastic Syndromes

Myelodysplastic Syndromes Clinical Trial

Official title:

iCare 2: Personalized Genomic Mutation Informed Treatment of Patients With Myelodysplastic Syndromes

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03446638
• Other study ID #: iCare 2
• Secondary ID: OCR17918IRB20170
• Status: Withdrawn
• Phase: N/A
• Start date: May 2019
• Est. completion date: September 2022

Study information

• Verified date: June 2019
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

It is hypothesized that personalized treatment informed by computational biology simulation technology will improve treatment outcomes for patients with relapsed or refractory MDS.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2022
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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:

1. 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

2. 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.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• FDA-approved drug or combination of drugs
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).
• FLAG induction
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.
• 7 + 3 induction
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.
• Low-dose cytarabine
Patients will receive 20 mg/m2 per day subcutaneously of cytarabine for 10 days every 28 days.

Other:
• Supportive care alone
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.

Device:
• Computational biology simulations software
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.

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	Cellworks Group Inc., Gateway for Cancer Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Differences in mutant allele frequencies between patients treated with computational biology-informed therapy and those treated with standard of care regimens		4 months
Other	Laboratory correlations between computational model and actual intracellular pathway activation status		4 months
Other	Clinical correlations between pharmacogenotypes and drug efficacy (as measured by IWG 2006 criteria for response in MDS)		4 months
Other	Clinical correlations between pharmacogenotypes and drug-related adverse events (as measured by CTCAE v4.0 criteria)		5 months
Primary	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
Secondary	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
Secondary	Difference in time to death between patients treated with computational biology-informed therapy and those treated with standard of care regimens		3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Difference in change in myeloblast percentage between patients treated with computational biology-informed therapy and those treated with standard of care regimens		4 months
Secondary	Difference in blood transfusion rate between patients treated with computational biology-informed therapy and those treated with standard of care regimens		7 months