IV Plerixafor With Mitoxantrone Etoposide and Cytarabine for Acute Myeloid Leukemia (AML)

The Washington University

Status and phase: Terminated; Phase 1

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: Cytarabine; Drug: Etoposide; Drug: Plerixafor; Drug: Mitoxantrone

Study type: Interventional

Funder types: Other

Identifiers

NCT01027923

09-1825 / 201101703

Details and patient eligibility

About

In this phase I extension study, the investigators seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.

Full description

In this study, we are seeking to target the leukemia microenvironment to overcome disease resistance. We hypothesize that by disrupting the interaction of leukemic blasts with the bone marrow microenvironment, we may sensitize leukemic blasts to the effects of cytotoxic chemotherapy. In current formulations, the volume of plerixafor required to administer doses higher than 240 mcg/kg may result in significant discomfort with repeated daily injections. In this phase I extension study, we seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.

Enrollment: 6 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Acute myeloid leukemia diagnosed according to WHO criteria with one of the following:

  • Primary refractory disease following ≥ 1 round of induction chemotherapy
  • First relapse or higher

• Age between 18 and 70 years

• ECOG performance status ≤ 2

• Adequate organ function defined as:

  • Creatinine ≤ 1.5 x institutional ULN
  • AST ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
  • ALT ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
  • Total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
  • Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram

• Women of childbearing potential and sexually active males must be willing and able to use effective contraception while on study

• Able to provide signed informed consent prior to registration on study

Exclusion criteria

• Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants)
• Peripheral blood blast count ≥ 50 x 103 /mm3
• Active CNS involvement with leukemia
• Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
• Pregnant or nursing
• Concurrently receiving any other investigational agent
• Received colony stimulating factors filgrastim or sargramostim within 48 hours or pegfilgrastim within 14 days of study
• Less than 2 weeks from the completion of any previous cytotoxic chemotherapy (excluding hydroxyurea)
• Severe concurrent illness that would limit compliance with study requirements

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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6 participants in 3 patient groups

Dose Level 1

Experimental group

Description:

Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5 Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5 Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5 Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

Treatment:

Drug: Mitoxantrone

Drug: Plerixafor

Drug: Etoposide

Drug: Cytarabine

Dose Level 2

Experimental group

Description:

Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5 Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5 Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5 Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

Treatment:

Drug: Mitoxantrone

Drug: Plerixafor

Drug: Etoposide

Drug: Cytarabine

Dose Level 3

Experimental group

Description:

Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5 Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5 Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5 Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5

Treatment:

Drug: Mitoxantrone

Drug: Plerixafor

Drug: Etoposide

Drug: Cytarabine