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

NCT01331590 | Completed Early Phase 1

• 1 other identifier: 201104323
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

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).

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Outcome Measures

Primary Outcomes (2)

• Treatment-related mortality

  30 days after start of treatment

• Delayed hematologic recovery

  Defined as neutrophil recovery (ANC \> 1,000/mm3) \> 42 days after the start of chemotherapy in the absence of persistent leukemia

  Day 46 of treatment

Secondary Outcomes (6)

• Complete remission rate cytogenetic complete remission

  42 days

• Overall survival

  2 years

• Disease-free survival

  2 years

• Remission duration

  2 years

• Frequency and severity of adverse events

  30 days post treatment

Study Arms (1)

G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna

EXPERIMENTAL

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; Drug: Ifosfamide; Drug: Etoposide; Drug: Dexamethasone; Drug: Mesna

Interventions

G-CSF DRUG

Also known as: Filgrastim, Neupogen, Granulocyte Colony-Stimulating Factor, Recombinant Methionyl Human G-CSF

G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna

Ifosfamide DRUG

Also known as: Ifex, Isophosphamide

G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna

Etoposide DRUG

Also known as: Etopophos, VP-16

G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna

Dexamethasone DRUG

Also known as: Decadron

G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna

Mesna DRUG

Also known as: Mesnex

G-CSF + Ifosfamide + Etoposide + Dexamethasone + Mesna

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (2)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; Ifosfamide; Etoposide; etoposide phosphate; Dexamethasone; Calcium Dobesilate; Mesna

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds

Study Officials

• Geoffrey Uy, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2011
• First Posted: April 8, 2011
• Study Start: July 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2015
• Last Updated: September 20, 2016

Record last verified: 2016-09

Locations

US (2)