Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia

Leukemia, Myeloid, Acute Clinical Trial

Official title:

Chemosensitization With Plerixafor Plus G-CSF in Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00906945
• Other study ID #: 10-0910 / 201106039
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: May 13, 2009
• Last updated: March 18, 2015
• Start date: February 2011
• Est. completion date: September 2015

Study information

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

Clinical Trial Summary

This study is designed to test the combination of Plerixafor with G-CSF for chemosensitization in patients with relapsed or refractory AML.

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 this study, we seek to maximize blockage of the SDF-1/CXCR4 axis through the following:

1. Addition of G-CSF, which down regulates SDF-1 expression and acts synergistically with plerixafor in stem cell mobilization

2. Intravenous instead of subcutaneous dosing of plerixafor to improve kinetics of administration.

3. Dose escalation of plerixafor and twice daily dosing to maintain maximum CXCR4 blockade.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 39
• Est. completion date: September 2015
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Acute myeloid leukemia diagnosed by WHO criteria with one of the following:

• Primary refractory disease following no more than 2 cycles of induction chemotherapy

• First relapse with no prior unsuccessful salvage chemotherapy

2. Age between 18 and 70 years old

3. ECOG performance status = 3

4. Adequate organ function defined as:

• Calculated creatinine clearance = 50 ml/min

• AST, ALT, total bilirubin = 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (eg. hepatic infiltration or biliary obstruction due to leukemia)

• Left ventricular ejection fraction of = 40% by MUGA scan or echocardiogram

5. Are surgically or biologically sterile or willing to practice acceptable birth control, as follows:

• Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative serum or urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device (IUD), transdermal/implanted or injected contraceptives and abstinence.

• Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during and for 3 months after the treatment period

6. Able to provide signed informed consent prior to registration on study

Exclusion Criteria:

1. Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants)

2. Peripheral blood blast count = 20 x 103 /mm3

3. Active CNS involvement with leukemia

4. Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide

5. Pregnant or nursing

6. Received any other investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within the preceding 2 weeks

7. Received colony stimulating factors filgrastim or sargramostim within 1 week or pegfilgrastim within 2 weeks of study

8. Severe concurrent illness that would limit compliance with study requirements

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• G-CSF

• Plerixafor

• Mitoxantrone

• Etoposide

• Cytarabine

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	Washington University	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	Phase I: To determine the maximum tolerated dose of plerixafor plus G-CSF when combined with MEC in patients with relapsed or refractory AML		45 days after start of treatment	Yes
Primary	Phase II: To determine the complete response rate (CR+CRi) for plerixafor plus G-CSF when combined with MEC in patients with relapsed or refractory AML.		45 days	No
Secondary	To determine the safety and tolerability.		30 days following end of treatment	Yes
Secondary	To determine the time to hematologic recovery		45 days after start of therapy	No
Secondary	To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.		8 days	No
Secondary	To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.		8 days	No
Secondary	To determine time to progression		Every 6 months for up to 2 years	No
Secondary	Determine time to treatment failure		8 days	No
Secondary	Determine overall survival		Every 6 months for 2 years	No

External Links

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