AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04263181
• Other study ID #: 201911201
• Status: Recruiting
• Start date: January 29, 2020
• Est. completion date: January 31, 2025

Study information

• Verified date: August 2023
• Source: Washington University School of Medicine
• Contact: Meagan Jacoby, M.D.
• Phone: 314-747-8439
• Email: mjacoby[@]wustl.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 165
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Myelodysplastic Syndromes

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Notable Labs

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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