Disrupting the Bone Marrow Microenvironment With G-CSF in Acute Lymphoblastic Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma Clinical Trial

Official title:

A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Relapsed or Refractory Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01331590
• Other study ID #: 201104323
• Status: Completed
• Phase: Phase 0
• First received: March 31, 2011
• Last updated: September 19, 2016
• Start date: July 2011
• Est. completion date: November 2015

Study information

• Verified date: September 2016
• 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

The purpose of this study is to determine the ability of G-CSF to disrupt the bone marrow microenvironment as a means to increase the efficacy of chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

Description:

In this study, we will combine G-CSF as priming prior to and during the administration of salvage chemotherapy regimen in ALL. Abundant data suggests that leukemic cells receive key growth and survival signals from the bone marrow microenvironment. Our preclinical data show that 4-5 days of G-CSF treatment is associated with a loss of osteoblasts and decreases expression of key chemokine/ cytokines which support lymphocyte development. The investigators hypothesize that G-CSF will disrupt the protective effects of the bone marrow microenvironment and augment the effect of chemotherapy in adults with ALL. This is a pilot study of G-CSF priming in adult patients with relapsed or refractory ALL to determine the feasibility and to characterize the effect of G-CSF treatment on the marrow microenvironment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: November 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Acute lymphoblastic leukemia diagnosed according to WHO criteria (>25% lymphoblasts in BM) which is relapsed or refractory to therapy. Patients with t(9;22) must be refractory to BCR-ABL tyrosine kinase inhibitors.

• Age = 18 years

• ECOG performance status = 3.

• Adequate organ function defined as:

• Calculated creatinine clearance = 50 ml/min

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

• 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:

• Previous salvage chemotherapy with ifosfamide and etoposide

• Pregnant or nursing

• Received any other investigational agent or cytotoxic chemotherapy within the preceding 2 weeks

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

• Severe concurrent illness that would limit compliance with study requirements

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• G-CSF

• Ifosfamide

• Etoposide

• Dexamethasone

• Mesna

Locations

Country	Name	City	State
United States	University of Chicago Medical Center	Chicago	Illinois
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	Treatment-related mortality		30 days after start of treatment	Yes
Primary	Delayed hematologic recovery	Defined as neutrophil recovery (ANC > 1,000/mm3) > 42 days after the start of chemotherapy in the absence of persistent leukemia	Day 46 of treatment	Yes
Secondary	Complete remission rate cytogenetic complete remission		42 days	No
Secondary	Overall survival	Every 6 months	2 years	No
Secondary	Disease-free survival	Every 6 months	2 years	No
Secondary	Remission duration	Every 6 months	2 years	No
Secondary	Frequency and severity of adverse events		30 days post treatment	Yes
Secondary	Interaction of pretreatment disease and patient characteristics on clinical outcomes	Morphology, cytogenetics, immunophenotype, WBC, and performance status	Baseline	No

External Links

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