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

Not Applicable

Withdrawn

• Conditions: Myelodysplastic Syndromes
• Interventions: Drug: FDA-approved drug or combination of drugs; Drug: FLAG induction; Device: Computational biology simulations software; Drug: 7 + 3 induction; Drug: Low-dose cytarabine; Other: Supportive care alone

• Registration Number: NCT03446638
• Lead Sponsor: University of Florida

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2018-02-20
• Study First Submitted QC: 2018-02-20
• Study First Posted: 2018-02-27
• Study Start: 2019-05
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-07
• Last Update Posted: 2019-06-11
• Primary Completion: 2021-08
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care Treatment	Low-dose cytarabine	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.
Computational Biology-Informed Treatment	Computational biology simulations software	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.
Standard of Care Treatment	Supportive care alone	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.
Standard of Care Treatment	7 + 3 induction	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.
Computational Biology-Informed Treatment	FDA-approved drug or combination of drugs	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.
Standard of Care Treatment	FLAG induction	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.

Primary Outcome Measures

Name	Time	Method
Difference in overall response, as measured by International Working Group (IWG) 2006 criteria for response in MDS	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 Outcome Measures

Name	Time	Method
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 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 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 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

Trial Locations

Locations (1)

University of Florida; 🇺🇸 Gainesville, Florida, United States