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

NCT ID: NCT01331590

Last Updated: 2016-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2015-11-30

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.

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna

G-CSF = 10 mcg/kg/d SQ starting on day 1 and continuing until ANC >=1000/mcL x 2 days

Ifosfamide = 3330 mg/m2/d CIVI over 24 hours on Days 4-6

Etoposide = 150 mg/m2 IV over 2 hours BID on Days 4-6

Dexamethasone = 5 mg/m2 PO or IV BID on Days 4-10

Mesna = 2660 mg/m2/d continuous IV infusion over 24 hours on Days 4-6. 2000 mg/m2 continuous IV infusion over 12 hours on Day 7 to be started immediately after completion of ifosfamide.

Group Type: EXPERIMENTAL

G-CSF

Intervention Type: DRUG

Ifosfamide

Intervention Type: DRUG

Etoposide

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Mesna

Intervention Type: DRUG

Interventions

G-CSF

Intervention Type: DRUG

Ifosfamide

Intervention Type: DRUG

Etoposide

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Mesna

Intervention Type: DRUG

Other Intervention Names

Filgrastim; Neupogen; Granulocyte Colony-Stimulating Factor; Recombinant Methionyl Human G-CSF; Ifex; Isophosphamide; Etopophos; VP-16; Decadron; Mesnex

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Geoffrey Uy, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

University of Chicago Medical Center

Chicago, Illinois, United States

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Related Links

http://www.siteman.wustl.edu

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

Other Identifiers

201104323

Identifier Type: -

Identifier Source: org_study_id