Precursor Cell Lymphoblastic Leukemia-Lymphoma
Conditions
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.
Interventions
DRUGG-CSF
DRUGIfosfamide
DRUGEtoposide
DRUGDexamethasone
DRUGMesna
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related mortality | 30 days after start of treatment | — |
| Delayed hematologic recovery | Day 46 of treatment | Defined as neutrophil recovery (ANC \> 1,000/mm3) \> 42 days after the start of chemotherapy in the absence of persistent leukemia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival | 2 years | Every 6 months |
| Remission duration | 2 years | Every 6 months |
| Complete remission rate cytogenetic complete remission | 42 days | — |
| Interaction of pretreatment disease and patient characteristics on clinical outcomes | Baseline | Morphology, cytogenetics, immunophenotype, WBC, and performance status |
| Frequency and severity of adverse events | 30 days post treatment | — |
| Overall survival | 2 years | Every 6 months |
Countries
United States
Outcome results
None listed