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NCT Number: NCT04263181

AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Acute Myeloid Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Peripheral blood draw

Procedure
  • All cohorts will have peripheral blood drawn at baseline no more than 4 days prior to the first dose of chemotherapy and must also occur before the first dose of chemotherapy
  • Cohort 0 or 1 - peripheral blood draw on Day 2
  • Cohorts 0, 2, 3, 4 and 5 - peripheral blood draw on Day 3
  • Cohort 0 or 1 - peripheral blood draw on Day 35 (at count recovery)
  • Cohorts 0, 2, 3, 4, and 5 - peripheral blood draw on Cycles 2 or 3 and 4 or 5, Day 28

Bone Marrow Aspirate

Procedure
  • Cohort 0 or 1 - bone marrow aspirate on Day 14
  • Cohort 0 or 1 - bone marrow aspirate on Day 35 (at count recovery)
  • Cohorts 0, 2, 3, 4, and 5 - bone marrow aspirate on Cycles 2 or 3 and 4 or 5, Day 28

Buccal swab

Procedure
  • Cohort 0 or 1 - buccal swab on Day 35 (at count recovery)
  • Cohorts 0, 2, 3, 4, and 5 - buccal swab on Cycle 2 or 3 and 4 or 5, Day 28

Primary outcomes

  1. 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

    Time frame: 90 days

Secondary outcomes

  1. 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

    Time frame: 90 days

  2. 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

    Time frame: 90 days

  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

    Time frame: 90 days

  4. 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

    Time frame: 1 year

  5. Determine whether reduced ex vivo drug sensitivity, as measured by a 384 well high throughput flow-based viability assay, correlates with reduced survival

    Time frame: 1 year

  6. 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

    Time frame: Day 3

  7. 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

    Time frame: Day 3

  8. 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

    Time frame: 90 days

  9. 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

    Time frame: Day 0

  10. 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

    Time frame: Day 3

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • Notable Labs

Registry information

Official study title

Identification of AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

Important dates

Study start
2020
Primary completion
2027
Study completion
2027
First posted
Feb 10, 2020
Registry last updated
Mar 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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