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

Leukemia, Myeloid, Acute Clinical Trial

— AML  

Official title:

A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01027923
• Other study ID #: 09-1825 / 201101703
• Status: Terminated
• Phase: Phase 1
• First received: December 7, 2009
• Last updated: January 21, 2015
• Start date: May 2010
• Est. completion date: September 2011

Study information

• Verified date: January 2015
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: September 2011
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Plerixafor

• Mitoxantrone

• Etoposide

• Cytarabine

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML.		Days 1-42 (all patients have to complete)	Yes
Secondary	To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML.		Between days 15-42	No
Secondary	To determine the safety and tolerability of plerixafor in combination with MEC		Minimum of 30 days following completion of treatment	Yes
Secondary	To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC.		Predose, 15 min, 30 min , and 10 hrs	No
Secondary	To determine the time to hematologic recovery		For up to 2 years	No
Secondary	To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.		Baseline, 6 hours	No
Secondary	To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.		Baseline, 6 hours	No
Secondary	To determine the time to overall survival		For up to 2 years	No
Secondary	To determine the time to event-free survival		For up to 2 years	No
Secondary	To determine the time to duration of remission		For up to 2 years	No
Secondary	To determine the time to relapse-free survival		For up to 2 years	No

External Links

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