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

Primary Purpose

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
G-CSF
Ifosfamide
Etoposide
Dexamethasone
Mesna
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Precursor Cell Lymphoblastic Leukemia-Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago Medical Center
  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna

Arm Description

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.

Outcomes

Primary Outcome Measures

Treatment-related mortality
Delayed hematologic recovery
Defined as neutrophil recovery (ANC > 1,000/mm3) > 42 days after the start of chemotherapy in the absence of persistent leukemia

Secondary Outcome Measures

Complete remission rate cytogenetic complete remission
Overall survival
Every 6 months
Disease-free survival
Every 6 months
Remission duration
Every 6 months
Frequency and severity of adverse events
Interaction of pretreatment disease and patient characteristics on clinical outcomes
Morphology, cytogenetics, immunophenotype, WBC, and performance status

Full Information

First Posted
March 31, 2011
Last Updated
September 19, 2016
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01331590
Brief Title
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

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Precursor Cell Lymphoblastic Leukemia-Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
G-CSF
Other Intervention Name(s)
Filgrastim, Neupogen, Granulocyte Colony-Stimulating Factor, Recombinant Methionyl Human G-CSF
Intervention Type
Drug
Intervention Name(s)
Ifosfamide
Other Intervention Name(s)
Ifex, Isophosphamide
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Etopophos, VP-16
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Decadron
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Mesnex
Primary Outcome Measure Information:
Title
Treatment-related mortality
Time Frame
30 days after start of treatment
Title
Delayed hematologic recovery
Description
Defined as neutrophil recovery (ANC > 1,000/mm3) > 42 days after the start of chemotherapy in the absence of persistent leukemia
Time Frame
Day 46 of treatment
Secondary Outcome Measure Information:
Title
Complete remission rate cytogenetic complete remission
Time Frame
42 days
Title
Overall survival
Description
Every 6 months
Time Frame
2 years
Title
Disease-free survival
Description
Every 6 months
Time Frame
2 years
Title
Remission duration
Description
Every 6 months
Time Frame
2 years
Title
Frequency and severity of adverse events
Time Frame
30 days post treatment
Title
Interaction of pretreatment disease and patient characteristics on clinical outcomes
Description
Morphology, cytogenetics, immunophenotype, WBC, and performance status
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Geoffrey Uy, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

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

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