Clinical trial NCT04263181: AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration
Official title: Identification of AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Notable Labs
First posted: 2020-02-10
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: -The study population consists of patients seen at Siteman Cancer Center.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 90 days
Secondary outcomes:
measure: 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
timeFrame: 90 days
measure: 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
timeFrame: 90 days
measure: 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
timeFrame: 90 days
measure: 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
timeFrame: 1 year
measure: Determine whether reduced ex vivo drug sensitivity, as measured by a 384 well high throughput flow-based viability assay, correlates with reduced survival
timeFrame: 1 year
measure: 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
timeFrame: Day 3
measure: 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
timeFrame: Day 3
measure: 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
timeFrame: 90 days
measure: 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
timeFrame: Day 0
measure: 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
timeFrame: Day 3
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Meagan Jacoby, M.D.
role: PRINCIPAL_INVESTIGATOR
References: