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

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ClinicalTrials.gov Identifier: NCT01331590
Recruitment Status : Completed
First Posted : April 8, 2011
Last Update Posted : September 20, 2016
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

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).

Condition or disease Intervention/treatment Phase
Precursor Cell Lymphoblastic Leukemia-Lymphoma Drug: G-CSF Drug: Ifosfamide Drug: Etoposide Drug: Dexamethasone Drug: Mesna Early Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Relapsed or Refractory Acute Lymphoblastic Leukemia
Study Start Date : July 2011
Actual Primary Completion Date : October 2014
Actual Study Completion Date : November 2015


Arm Intervention/treatment
Experimental: 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.

Drug: G-CSF
Other Names:
  • Filgrastim
  • Neupogen
  • Granulocyte Colony-Stimulating Factor
  • Recombinant Methionyl Human G-CSF

Drug: Ifosfamide
Other Names:
  • Ifex
  • Isophosphamide

Drug: Etoposide
Other Names:
  • Etopophos
  • VP-16

Drug: Dexamethasone
Other Name: Decadron

Drug: Mesna
Other Name: Mesnex




Primary Outcome Measures :
  1. Treatment-related mortality [ Time Frame: 30 days after start of treatment ]
  2. Delayed hematologic recovery [ Time Frame: 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 Outcome Measures :
  1. Complete remission rate cytogenetic complete remission [ Time Frame: 42 days ]
  2. Overall survival [ Time Frame: 2 years ]
    Every 6 months

  3. Disease-free survival [ Time Frame: 2 years ]
    Every 6 months

  4. Remission duration [ Time Frame: 2 years ]
    Every 6 months

  5. Frequency and severity of adverse events [ Time Frame: 30 days post treatment ]
  6. Interaction of pretreatment disease and patient characteristics on clinical outcomes [ Time Frame: Baseline ]
    Morphology, cytogenetics, immunophenotype, WBC, and performance status



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01331590


Locations
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Geoffrey Uy, M.D. Washington University School of Medicine

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01331590     History of Changes
Other Study ID Numbers: 201104323
First Posted: April 8, 2011    Key Record Dates
Last Update Posted: September 20, 2016
Last Verified: September 2016

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Etoposide phosphate
Isophosphamide mustard
Etoposide
Ifosfamide
BB 1101
Lenograstim
Mesna
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors