AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

Identification of 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Intervention / Treatment: Procedure: Peripheral blood draw; Procedure: Bone marrow aspirate; Procedure: Buccal swab

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

-The study population consists of patients seen at Siteman Cancer Center.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 0; -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.	Procedure: Peripheral blood draw; 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; Procedure: Bone marrow aspirate; 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; Procedure: Buccal swab; 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
Cohort 1; 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).	Procedure: Peripheral blood draw; 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; Procedure: Bone marrow aspirate; 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; Procedure: Buccal swab; 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
Cohort 2; 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.	Procedure: Peripheral blood draw; 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; Procedure: Bone marrow aspirate; 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; Procedure: Buccal swab; 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
Cohort 3; 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	Procedure: Peripheral blood draw; 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; Procedure: Bone marrow aspirate; 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; Procedure: Buccal swab; 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
Cohort 4; 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.	Procedure: Peripheral blood draw; 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; Procedure: Bone marrow aspirate; 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; Procedure: Buccal swab; 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
Cohort 5; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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 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 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 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
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 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 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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Notable Labs
• Investigators: Principal Investigator: Meagan Jacoby, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: February 6, 2020
• First Submitted That Met QC Criteria: February 6, 2020
• First Posted (Actual): February 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
• Other Study ID Numbers: 201911201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Blood, buccal cells, and data will be shared. The researchers may be doing research at Washington University, at other research centers and institutions, or industry sponsors of research. Data may also be shared with large data repositories. The researchers may be doing research in areas similar to this research or in other unrelated areas.
• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication.
• IPD Sharing Access Criteria: Proposals should be submitted directly to jwelch@wustl.edu.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No