AzTrials
AzTrials

Myelodysplastic SyndromesPhase 1MDSNCT01065129

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

A Phase 1 study testing G-CSF, Plerixafor and Azacitidine in people with Myelodysplastic Syndromes, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
G-CSF, Plerixafor and Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
2 Sep 2010to 18 Oct 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 13Show fewer
  • 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.

Who cannot join

  • 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.)
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I Trial Evaluating the Effects of Plerixafor (AMD3100) and G-CSF in Combination With Azacitidine (Vidaza) for the Treatment of MDS

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.

Read the detailed description

The interaction of normal stem cells with the bone marrow microenvironment is mediated by a number of factors. These interactions have been implicated in protecting malignant hematopoietic cells from spontaneous apoptosis and genotoxic stresses such as chemotherapy. Key elements are CXCR4, which is expressed on normal stem cells and leukemic blasts, and its ligand, stromal derived factor 1 (SDF-1) expressed by bone marrow stromal cells and osteoblasts. The CXCR4/SDF-1 axis is essential for homing, retention and mobilization of stem cells from the bone marrow microenvironment. Plerixafor is a bicyclam small molecule inhibitor of CXCR4 and has been extensively studied by our group and others as a potent stem cell mobilization agent both in combination with G-CSF or alone (25, 62). Plerixafor is currently being investigated in a phase I/II trial in combination with salvage chemotherapy for relapsed AML in an attempt to sensitize leukemia stem cells to chemotherapy. The goal of this study is to determine the optimal dose of plerixafor for the treatment of patients with high-risk myelodysplastic syndrome (MDS) in combination with G-CSF and azacitidine. We hypothesize that plerixafor in combination with G-CSF will detach MDS blasts from the bone marrow microenvironment resulting in their increased proliferation and sensitivity to azacitidine; thus, improving complete and partial response rates (CR/PR).

Being tested
G-CSF, Plerixafor, Azacitidine
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • G-CSFDrug

    Also called Neupogen, Filgrastim

  • PlerixaforDrug

    Also called Mozobil

  • AzacitidineDrug

    Also called Vidaza, 5-azacytidine

Study groups in NCT01065129
Study groupRoleWhat they receive
Dose Level 1ExperimentalAMD3100 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.
Receives: Drug: G-CSF; Drug: Plerixafor; Drug: Azacitidine
Dose Level 2ExperimentalAMD3100 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.
Receives: Drug: G-CSF; Drug: Plerixafor; Drug: Azacitidine
Dose Level 3ExperimentalAMD3100 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.
Receives: Drug: G-CSF; Drug: Plerixafor; Drug: Azacitidine
Expanded DLT CohortExperimentalAfter 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.
Receives: Drug: Plerixafor; Drug: Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 42 days after the start of the second cycle of treatment

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

    Measured: 30 days post-treatment

Secondary outcomes (4)

  1. Characterize the mobilization of MDS cells

    Measured: Cycle 1 Day 5

  2. Determine the pharmacokinetics of plerixafor on azacitidine

    Measured: Cycle 1 Day 5

  3. Determine progression free survival and response rates

    Measured: 2 years

  4. Freedom from transfusion

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2010 (estimated)
  2. Study start2 Sep 2010
  3. Primary completionJul 2014
  4. Study completion18 Oct 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01065129
Sponsor's protocol ID
10-0150 / 201101810
Acronym
MDS
Status last verified
Mar 2017
First submitted
5 Feb 2010
Last updated
20 Mar 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing G-CSF, Plerixafor and Azacitidine in people with Myelodysplastic Syndromes, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the optimal dose and schedule of plerixafor + G-CSF and azacitidine in patients with MDS (time frame: 42 days after the start of the second cycle of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01065129.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in