Clinical trial NCT01331590: Disrupting the Bone Marrow Microenvironment With G-CSF in Acute Lymphoblastic Leukemia
Official title: A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Relapsed or Refractory Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2011-04-08
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-related mortality
timeFrame: 30 days after start of treatment
measure: Delayed hematologic recovery
timeFrame: Day 46 of treatment
Secondary outcomes:
measure: Complete remission rate cytogenetic complete remission
timeFrame: 42 days
measure: Overall survival
timeFrame: 2 years
measure: Disease-free survival
timeFrame: 2 years
measure: Remission duration
timeFrame: 2 years
measure: Frequency and severity of adverse events
timeFrame: 30 days post treatment
measure: Interaction of pretreatment disease and patient characteristics on clinical outcomes
timeFrame: Baseline
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
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: