Plerixafor and Granulocyte Colony-stimulating Factor (G-CSF) in Combination With Azacitidine for the Treatment of Myelodysplastic Syndrome (MDS)

NCT01065129 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 10-0150 / 201101810
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Our main objectives are to determine the optimal dose and schedule of plerixafor + G-CSF and azacitidine in patients with MDS and determine the safety and tolerability of plerixafor + G-CSF and azacitidine.

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

• Determine the optimal dose and schedule of plerixafor + G-CSF and azacitidine in patients with MDS

  The observation period for bone marrow aplasia as a DLT will be 42 days after the start of the second cycle of treatment or until the documentation of progression to leukemia. For all other toxicities, the DLT observation period will be 28 days from the start of treatment.

  42 days after the start of the second cycle of treatment

• Determine the safety and tolerability of plerixafor + G-CSF and azacitidine

  30 days post-treatment

Secondary Outcomes (4)

• Characterize the mobilization of MDS cells

  Cycle 1 Day 5

• Determine the pharmacokinetics of plerixafor on azacitidine

  Cycle 1 Day 5

• Determine progression free survival and response rates

  2 years

• Freedom from transfusion

  2 years

Study Arms (4)

Dose Level 1

EXPERIMENTAL

AMD3100 320 μg/kg SC Days 1-5 of each 28 day cycle. Azacitidine 75 mg/m2 SC Days 1-5 of each 28 days cycle. G-CSF 5 μg/k SC Days 1-5 of each 28 days cycle.

Drug: G-CSF; Drug: Plerixafor; Drug: Azacitidine

Dose Level 2

EXPERIMENTAL

AMD3100 440 μg/kg SC Days 1-5 of each 28 day cycle. Azacitidine 75 mg/m2 SC Days 1-5 of each 28 days cycle. G-CSF 5 μg/k SC Days 1-5 of each 28 days cycle.

Drug: G-CSF; Drug: Plerixafor; Drug: Azacitidine

Dose Level 3

EXPERIMENTAL

AMD3100 560 μg/kg SC Days 1-5 of each 28 day cycle. Azacitidine 75 mg/m2 SC Days 1-5 of each 28 days cycle. G-CSF 5 μg/k SC Days 1-5 of each 28 days cycle.

Drug: G-CSF; Drug: Plerixafor; Drug: Azacitidine

Expanded DLT Cohort

EXPERIMENTAL

After the MTD is determined, patients will be enrolled at the MTD dose of plerixafor. These patients will not receive G-CSF priming but will be treated with plerixafor and azacitidine for 2 cycles.

Drug: Plerixafor; Drug: Azacitidine

Interventions

G-CSF DRUG

Also known as: Neupogen, Filgrastim

Dose Level 1; Dose Level 2; Dose Level 3

Plerixafor DRUG

Also known as: Mozobil

Dose Level 1; Dose Level 2; Dose Level 3; Expanded DLT Cohort

Azacitidine DRUG

Also known as: Vidaza, 5-azacytidine

Dose Level 1; Dose Level 2; Dose Level 3; Expanded DLT Cohort

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed MDS with 5-20% blasts on bone marrow aspirate at the time of study enrollment AND at least one cytopenia.
• MDS is defined by the WHO criteria
• Previous therapy with decitabine or azacitidine will be allowed but patients must be at least 4 weeks from prior chemotherapy or radiation.
• Age \>=18 years. Because no dosing or adverse event data are currently available on the use of plerixafor in combination with G-CSF or azacitidine in patients \<18 years of age, children are excluded from this study; however, they will be eligible for future pediatric phase II combination trials.
• Life expectancy of greater than 2 months.
• ECOG performance status \<= 2 (Karnofsky \>=60%; see Appendix 1).
• Patients must have normal organ function as defined below:
• total bilirubin ≤ 1.5 X institutional upper limit of normal
• AST ≤ 2.0 X institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance \>=60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Ability of the patient (or legally authorized representative, if applicable) to understand and the willingness to sign a written informed consent document.
• Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative serum or urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device (IUD), transdermal/implanted or injected contraceptives and abstinence. Males must agree to abstain from sexual activity or agree to utilize a medically approved contraception method during and for 3 months after the treatment period. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Patients with untreated 5q minus syndrome MDS
• Patients who have had G-CSF or GM-CSF within 2 weeks of the start of study
• Patients receiving any other investigational agents.
• Patients with known brain metastases. (These patients should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.)
• History of severe allergic or anaphylactic reactions attributed to compounds of similar chemical or biologic composition to plerixafor, azacitidine, G-CSF, or mannitol.
• History of sickle cell anemia. (G-CSF may initiate pain crises.)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because plerixafor, G-CSF, and azacitidine are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azacitidine, G-CSF, or plerixafor, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
• Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with plerixafor. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Patients with advanced malignant hepatic tumors
• History of cardiac arrhythmia

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

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

Myelodysplastic Syndromes

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; plerixafor; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic 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; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Mark Schroeder, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2010
• First Posted: February 9, 2010
• Study Start: September 2, 2010
• Primary Completion: July 1, 2014
• Study Completion: October 18, 2016
• Last Updated: March 20, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)