Clinical trial NCT01027923: IV Plerixafor With Mitoxantrone Etoposide and Cytarabine for Acute Myeloid Leukemia (AML)
Official title: A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2009-12-09
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML.
timeFrame: Days 1-42 (all patients have to complete)
Secondary outcomes:
measure: To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML.
timeFrame: Between days 15-42
measure: To determine the safety and tolerability of plerixafor in combination with MEC
timeFrame: Minimum of 30 days following completion of treatment
measure: To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC.
timeFrame: Predose, 15 min, 30 min , and 10 hrs
measure: To determine the time to hematologic recovery
timeFrame: For up to 2 years
measure: To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.
timeFrame: Baseline, 6 hours
measure: To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.
timeFrame: Baseline, 6 hours
measure: To determine the time to overall survival
timeFrame: For up to 2 years
measure: To determine the time to event-free survival
timeFrame: For up to 2 years
measure: To determine the time to duration of remission
timeFrame: For up to 2 years
measure: To determine the time to relapse-free survival
timeFrame: For up to 2 years
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Geoffrey Uy, M.D.
role: PRINCIPAL_INVESTIGATOR
References: