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

Primary Purpose

Myelodysplastic Syndromes

Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
FDA-approved drug or combination of drugs
FLAG induction
7 + 3 induction
Low-dose cytarabine
Supportive care alone
Computational biology simulations software
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring myelodysplastic syndromes, MDS, computational biology, relapsed, refractory

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Computational Biology-Informed Treatment

Standard of Care Treatment

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Difference in time to death between patients treated with computational biology-informed therapy and those treated with standard of care regimens
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
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
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
Difference in change in myeloblast percentage between patients treated with computational biology-informed therapy and those treated with standard of care regimens
Difference in blood transfusion rate between patients treated with computational biology-informed therapy and those treated with standard of care regimens

Full Information

First Posted
February 20, 2018
Last Updated
June 7, 2019
Sponsor
University of Florida
Collaborators
Gateway for Cancer Research, Cellworks Group Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03446638
Brief Title
iCare 2: Personalized Genomic Mutation Informed Treatment of Patients With Myelodysplastic Syndromes
Official Title
iCare 2: Personalized Genomic Mutation Informed Treatment of Patients With Myelodysplastic Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Withdrawn
Why Stopped
administratively withdrawn
Study Start Date
May 2019 (Anticipated)
Primary Completion Date
August 2021 (Anticipated)
Study Completion Date
September 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
Gateway for Cancer Research, Cellworks Group Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
myelodysplastic syndromes, MDS, computational biology, relapsed, refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Computational Biology-Informed Treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard of Care Treatment
Arm Type
Active Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
FDA-approved drug or combination of drugs
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
FLAG induction
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
7 + 3 induction
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Low-dose cytarabine
Intervention Description
Patients will receive 20 mg/m2 per day subcutaneously of cytarabine for 10 days every 28 days.
Intervention Type
Other
Intervention Name(s)
Supportive care alone
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Computational biology simulations software
Intervention Description
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.
Primary Outcome Measure Information:
Title
Difference in overall response, as measured by International Working Group (IWG) 2006 criteria for response in MDS
Description
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
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Difference in safety and feasibility, as measured by CTCAE v4.0 criteria
Description
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
Time Frame
5 months
Title
Difference in time to death between patients treated with computational biology-informed therapy and those treated with standard of care regimens
Time Frame
3 years
Title
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
Time Frame
4 months
Title
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
Time Frame
4 months
Title
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
Time Frame
4 months
Title
Difference in change in myeloblast percentage between patients treated with computational biology-informed therapy and those treated with standard of care regimens
Time Frame
4 months
Title
Difference in blood transfusion rate between patients treated with computational biology-informed therapy and those treated with standard of care regimens
Time Frame
7 months
Other Pre-specified Outcome Measures:
Title
Differences in mutant allele frequencies between patients treated with computational biology-informed therapy and those treated with standard of care regimens
Time Frame
4 months
Title
Laboratory correlations between computational model and actual intracellular pathway activation status
Time Frame
4 months
Title
Clinical correlations between pharmacogenotypes and drug efficacy (as measured by IWG 2006 criteria for response in MDS)
Time Frame
4 months
Title
Clinical correlations between pharmacogenotypes and drug-related adverse events (as measured by CTCAE v4.0 criteria)
Time Frame
5 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Cogle, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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