AML/MDS Drug Sensitization by in Vivo Chemotherapy Administration

The Washington University

Status: Active, not recruiting

Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia

Treatments: Procedure: Buccal swab; Procedure: Peripheral blood draw; Procedure: Bone marrow aspirate

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT04263181

201911201

Details and patient eligibility

About

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.

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

80 participants in 6 patient groups

Cohort 0

Description:

-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.

Treatment:

Procedure: Bone marrow aspirate

Procedure: Buccal swab

Procedure: Peripheral blood draw

Cohort 1

Description:

* 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).

Treatment:

Procedure: Bone marrow aspirate

Procedure: Buccal swab

Procedure: Peripheral blood draw

Cohort 2

Description:

* 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.

Treatment:

Procedure: Bone marrow aspirate

Procedure: Buccal swab

Procedure: Peripheral blood draw

Cohort 3

Description:

* 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

Treatment:

Procedure: Bone marrow aspirate

Procedure: Buccal swab

Procedure: Peripheral blood draw

Cohort 4

Description:

* 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.

Treatment:

Procedure: Bone marrow aspirate

Procedure: Buccal swab

Procedure: Peripheral blood draw

Cohort 5

Description:

* 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.