AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

Active, not recruiting

• Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia

• Registration Number: NCT04263181
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-29
• Study First Submitted: 2020-02-06
• Study First Submitted QC: 2020-02-06
• Study First Posted: 2020-02-10
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-02-27
• Primary Completion: 2026-01-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

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

• Peripheral blood blasts > 1%

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

• Age ≥ 18 years

• Anticipated treatment with any of the following regimens (Cohort 0) or:

  • Cohort 1: A standard induction protocol with infusional cytarabine
  • Cohort 2: Decitabine (either 5-day or 10-day regimens)
  • Cohort 3: Azacitidine (either intravenous or subcutaneous administration)
  • Cohort 4: Decitabine (either 5-day or 10-day) + venetoclax
  • Cohort 5: Azacitidine (either intravenous or subcutaneous administration on 7 day or 5+2+2 schedule) + venetoclax

• Patients may receive these therapies as part of other on-going clinical trials or as standard of care treatment.

• Patients in Cohort 1 may receive SOC midostaurin or gemtuzumab ozogamicin, provided these start after the Day 2 sample is collected. Patients in Cohort 1 may receive a standard combination of cytarabine/idarubicin, cytarabine/daunorubicin, or Vyxeos, a liposomal formulation of cytarabine and daunorubicin.

• ECOG performance status ≤ 3

• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria

• Pregnant or currently nursing
• Prior chemotherapy with hypomethylating agents
• Known history of positive HIV serology.
• Known positive Hepatitis C serology.
• Patient must not have received any chemotherapy within 7 days of enrollment, and any acute treatment-related toxicities must have returned to baseline. Patients may have received hydrea as long as they fulfill peripheral blood blast and peripheral WBC inclusion criteria. Prior TKI therapy is allowed, but must be discontinued within 3 days of baseline blood collection.
• Currently receiving any other investigational agents.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Determine whether ex vivo drug sensitivity obtained for Day 0 ex vivo treatments for all cohorts as measured by a 384 well high throughput flow-based viability assay correlates with clinical assay	90 days

Secondary Outcome Measures

Name	Time	Method
Ex vivo drug sensitivity obtained for Day 0 ex vivo treatments as measured by a 384 well high throughput flow-based viability assay correlates with molecular responses as measured by founding clone mutation reduction <2% and exome sequencing	90 days
Determine whether MDS and AML have overlapping or unique profiles in ex vivo drug sensitivity, as measured by a 384 well high throughput flow-based viability assay	Day 0
Determine whether MDS and AML have overlapping or unique profiles in ex vivo drug sensitivity as measured by a 384 well high throughput flow-based viability assay	Day 3
Determine whether reduced ex vivo drug sensitivity on day 2 (cohorts 0 or 1) or day 3 (cohorts 2, 3, 4, and 5), as measured by a 384 well high throughput flow-based viability assay, correlates with reduced molecular responses	90 days
Determine whether ex vivo drug sensitivity, as measured by a 384 well high throughput flow-based viability assay, correlates with the presence of clinically available mutations, as measured by exome sequencing	90 days
Determine whether in vivo chemotherapy leads to increased ex vivo sensitivity to any class of drugs in more than 20% of patients treated on any study arm as measured by a 384 well high throughput flow-based viability assay	Day 3
Determine whether decitabine and azacitidine are associated with overlapping or unique profiles in drug sensitivity changes as measured by a 384 well high throughput flow-based viability assay	Day 3
Determine whether an increase in ex vivo drug resistance on day 2 (cohorts 0 or 1) or day 3 (cohorts 2, 3, 4 and 5), as measured by a 384 well high-throughput flow-based viability assay, correlates with reduced clinical responses	90 days
Determine whether reduced drug ex vivo drug sensitivity on day 2 (cohorts 0 or 1) or 3 (cohorts 2, 3, 4, and 5), as measured by a 384 well high throughput flow-based viability assay, correlates with reduced disease-free survival	1 year
Determine whether reduced ex vivo drug sensitivity, as measured by a 384 well high throughput flow-based viability assay, correlates with reduced survival	1 year

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States