AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

Overseen By Meagan Jacoby, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must be taking: Cytarabine, Decitabine, Azacitidine, Venetoclax

Must not be taking: Investigational agents

Disqualifiers: Pregnant, HIV, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles

80 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, the investigators will explore the feasibility of ex vivo drug screening to predict sensitivity to chemotherapy resistance and to identify novel synergy between chemotherapies.

Research Team

Meagan Jacoby, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Inclusion Criteria

Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Peripheral blood blasts > 1%

Peripheral white blood cell count > 1,000/µl.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy treatment based on their assigned cohort, including cytarabine/idarubicin, decitabine, azacitidine, and combinations with venetoclax

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bone marrow aspirate
• Buccal swab
• Peripheral blood draw

Participant Groups

Group I: Cohort 5 Experimental Treatment 0 Interventions

* Patients treated with azacitidine + venetoclax * Patients will receive azacitidine 75 mg/m2/day as a 1-hour infusion or by subcutaneous injection on consecutive Days 1-7 or on day 1-5 and 8-9 (per treating physician discretion) of each 28-day cycle. Patients will receive venetoclax PO 100 mg on Day 1, 200 mg on Day 2, and 400 mg daily thereafter.

Group II: Cohort 4 Experimental Treatment 3 Interventions

* Patients treated with decitabine + venetoclax * Patients will receive decitabine 20 mg/m2/day as a 1-hour infusion on consecutive Days 1-5 or 1-10 (per treating physician discretion) of each 28-day cycle. Patients will receive venetoclax PO 100 mg on Day 1, 200 mg on Day 2, and 400 mg daily thereafter.

Group III: Cohort 3 Experimental Treatment 3 Interventions

* Patients treated with azacitidine * Patients will receive azacitidine 75 mg/m2/day as a subcutaneous injection on Days 1-7 or on day 1-5 and 8-9 (per treating physician discretion) of each 28-day cycle

Group IV: Cohort 2 Experimental Treatment 3 Interventions

* Patients treated with decitabine * Patients will receive decitabine 20 mg/m2/day as a 1-hour infusion on consecutive Days 1-5 or 1-10 (per treating physician discretion) of each 28-day cycle.

Group V: Cohort 1 Experimental Treatment 3 Interventions

* Patients treated with cytarabine/idarubicin induction therapy * Patients will receive a standard cytarabine/idarubicin induction, which includes cytarabine 200 mg/m2 CIVI in 0.9% normal saline over 24 hours for 7 consecutive days (Days 1-7) and idarubicin 12 mg/m2 per day in 0.9% normal saline over 15-30 minutes for 3 consecutive days (Days 1-3). Other standard cytarabine-based induction protocols are allowed (e.g. cytarabine/daunorubicin or Vyxeos).

Group VI: Cohort 0 Experimental Treatment 3 Interventions

-A technical run-in of 5 patients with any of the following: * Standard cytarabine/idarubicin induction, includes cytarabine 200 mg/m2 CIVI in 0.9% normal saline over 24 hours for 7 consecutive days (Days 1-7) \& idarubicin 12 mg/m2 per day for 3 consecutive days (Days 1-3). Other standard cytarabine-based induction protocols are allowed * Decitabine 20 mg/m2/day as a 1-hour infusion on consecutive Days 1-5 or 1-10 of each 28-day cycle. * Azacitidine 75 mg/m2/day as a subcutaneous injection on Days 1-7 or on day 1-5 and 8-9 of each 28-day cycle * Decitabine 20 mg/m2/day as a 1-hour infusion on consecutive Days 1-5 or 1-10 of each 28-day cycle. Patients will receive venetoclax PO 100 mg on Day 1, 200 mg on Day 2, and 400 mg daily thereafter. * Azacitidine 75 mg/m2/day as a 1-hour infusion or by subcutaneous injection on consecutive Days 1-7 or on day 1-5 and 8-9 of each 28-day cycle. Patients will receive venetoclax PO 100 mg on Day 1, 200 mg on Day 2, and 400 mg daily thereafter.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Notable Labs

Industry Sponsor

Trials

2

Recruited

200+