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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01331590
First received: March 31, 2011
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

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 Intervention
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug: G-CSF
Drug: Ifosfamide
Drug: Etoposide
Drug: Dexamethasone
Drug: Mesna

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Treatment-related mortality [ Time Frame: 30 days after start of treatment ] [ Designated as safety issue: Yes ]
  • Delayed hematologic recovery [ Time Frame: Day 46 of treatment ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 42 days ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Every 6 months

  • Disease-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Every 6 months

  • Remission duration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Every 6 months

  • Frequency and severity of adverse events [ Time Frame: 30 days post treatment ] [ Designated as safety issue: Yes ]
  • Interaction of pretreatment disease and patient characteristics on clinical outcomes [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Morphology, cytogenetics, immunophenotype, WBC, and performance status


Enrollment: 13
Study Start Date: July 2011
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01331590     History of Changes
Other Study ID Numbers: 201104323
Study First Received: March 31, 2011
Last Updated: September 11, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Etoposide
Etoposide phosphate
Ifosfamide
Isophosphamide mustard
Lenograstim
Adjuvants, Immunologic
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on October 21, 2014