AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

NCT ID: NCT04263181

Last Updated: 2025-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-01-29

Study Completion Date

2026-01-31

Brief Summary

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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

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Conditions

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Acute Myeloid Leukemia Myelodysplastic Syndromes

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Peripheral blood draw

Intervention Type 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

Intervention Type 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

Intervention Type 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

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).

Peripheral blood draw

Intervention Type 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

Intervention Type 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

Intervention Type 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

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.

Peripheral blood draw

Intervention Type 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

Intervention Type 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

Intervention Type 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

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

Peripheral blood draw

Intervention Type 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

Intervention Type 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

Intervention Type 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

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.

Peripheral blood draw

Intervention Type 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

Intervention Type 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

Intervention Type 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

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.

No interventions assigned to this group

Interventions

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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

Intervention Type 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

Intervention Type 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

Intervention Type PROCEDURE

Eligibility Criteria

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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.

* Currently receiving any other investigational agents.

Exclusion Criteria

* Pregnant or currently nursing
* Prior chemotherapy with hypomethylating agents
* Known history of positive HIV serology.
* Known positive Hepatitis C serology.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Notable Labs

INDUSTRY

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Meagan Jacoby, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Countries

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United States

Related Links

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http://www.siteman.wustl.edu

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

Other Identifiers

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201911201

Identifier Type: -

Identifier Source: org_study_id

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