Leukemia, Myeloid, AcutePhase 1AMLNCT01027923
IV Plerixafor With Mitoxantrone Etoposide and Cytarabine for Acute Myeloid Leukemia (AML)
A Phase 1 study testing Plerixafor, Mitoxantrone and Etoposide in people with Leukemia, Myeloid, Acute, run by Washington University School of Medicine at 1 site in United States.
Trial summary
In this phase I extension study, the investigators seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- Plerixafor, Mitoxantrone and Etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Sep 2011
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute myeloid leukemia diagnosed according to WHO criteria with one of the following:
- Primary refractory disease following ≥ 1 round of induction chemotherapy
- First relapse or higher
- Age between 18 and 70 years
- ECOG performance status ≤ 2
- Adequate organ function defined as:
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- Creatinine ≤ 1.5 x institutional ULN
- AST ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
- ALT ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
- Total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (e.g., hepatic infiltration or biliary obstruction due to leukemia)
- Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram
- 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
Who cannot join
- Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants)
- Peripheral blood blast count ≥ 50 x 103 /mm3
- Active CNS involvement with leukemia
- Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
- Pregnant or nursing
- Concurrently receiving any other investigational agent
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- Received colony stimulating factors filgrastim or sargramostim within 48 hours or pegfilgrastim within 14 days of study
- Less than 2 weeks from the completion of any previous cytotoxic chemotherapy (excluding hydroxyurea)
- Severe concurrent illness that would limit compliance with study requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia
In this phase I extension study, the investigators seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.
Read the detailed description
In this study, we are seeking to target the leukemia microenvironment to overcome disease resistance. We hypothesize that by disrupting the interaction of leukemic blasts with the bone marrow microenvironment, we may sensitize leukemic blasts to the effects of cytotoxic chemotherapy. In current formulations, the volume of plerixafor required to administer doses higher than 240 mcg/kg may result in significant discomfort with repeated daily injections. In this phase I extension study, we seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Plerixafor, Mitoxantrone, Etoposide, Cytarabine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlerixaforDrug
Also called AMD3100, Mozobil
MitoxantroneDrug
Also called Novantrone
EtoposideDrug
Also called Etopophos, Toposar, VePesid, VP156
CytarabineDrug
Also called Cytosar-U, Ara-C, Cytosine arabinoside
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5 Receives: Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine |
| Dose Level 2 | Experimental | Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5 Receives: Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine |
| Dose Level 3 | Experimental | Mitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5
Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5
Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5
Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5 Receives: Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML.
Measured: Days 1-42 (all patients have to complete)
Secondary outcomes (10)
To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML.
Measured: Between days 15-42
To determine the safety and tolerability of plerixafor in combination with MEC
Measured: Minimum of 30 days following completion of treatment
To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC.
Measured: Predose, 15 min, 30 min , and 10 hrs
To determine the time to hematologic recovery
Measured: For up to 2 years
To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.
Measured: Baseline, 6 hours
To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.
Measured: Baseline, 6 hours
To determine the time to overall survival
Measured: For up to 2 years
To determine the time to event-free survival
Measured: For up to 2 years
To determine the time to duration of remission
Measured: For up to 2 years
To determine the time to relapse-free survival
Measured: For up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2009 (estimated)
- Study startMay 2010
- Primary completionJul 2010
- Study completionSep 2011
Why it stopped: Withdrawal of support from sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Geoffrey Uy, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01027923
- Sponsor's protocol ID
- 09-1825 / 201101703
- Acronym
- AML
- Status last verified
- Jan 2015
- First submitted
- 7 Dec 2009
- Last updated
- 26 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Intravenous Plerixafor in Combination With Mitoxantrone Etoposide and Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT01027923
- Acronym / sponsor ID
- AML / 09-1825 / 201101703
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawal of support from sponsor
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- Jul 2010 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 9 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this phase I extension study, the investigators seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.
Detailed description
In this study, we are seeking to target the leukemia microenvironment to overcome disease resistance. We hypothesize that by disrupting the interaction of leukemic blasts with the bone marrow microenvironment, we may sensitize leukemic blasts to the effects of cytotoxic chemotherapy. In current formulations, the volume of plerixafor required to administer doses higher than 240 mcg/kg may result in significant discomfort with repeated daily injections. In this phase I extension study, we seek to test the safety of both higher doses of plerixafor as well as intravenous dosing to maximize inhibition of the target, CXCR4.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Drug: Plerixafor, Drug: Mitoxantrone, Drug: Etoposide, Drug: CytarabineMitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5 Plerixafor 320 mcg/kg/day IV over 30 minutes on days 0-5 Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5 Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5 |
| Dose Level 2 | Experimental | Drug: Plerixafor, Drug: Mitoxantrone, Drug: Etoposide, Drug: CytarabineMitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5 Plerixafor 420 mcg/kg/day IV over 30 minutes on days 0-5 Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5 Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5 |
| Dose Level 3 | Experimental | Drug: Plerixafor, Drug: Mitoxantrone, Drug: Etoposide, Drug: CytarabineMitoxantrone 8 mg/m2/day IV over 30 minutes once daily on days 1-5 Plerixafor 560 mcg/kg/day IV over 30 minutes on days 0-5 Etoposide 100 mg/m2/day IV over 60 minutes once daily on days 1-5 Cytarabine 1000 mg/m2/day IV over 60 minutes once daily on days 1-5 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Acute myeloid leukemia diagnosed according to WHO criteria with one of the following:
- Age between 18 and 70 years
- ECOG performance status ≤ 2
- Adequate organ function defined as:
- Women of childbearing potential and sexually active males must be willing and able to use effective contraception while on study
Key exclusion criteria (9 listed)
- Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants)
- Peripheral blood blast count ≥ 50 x 103 /mm3
- Active CNS involvement with leukemia
- Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
- Pregnant or nursing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlerixaforAlso: AMD3100, Mozobil | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| MitoxantroneAlso: Novantrone | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| EtoposideAlso: Etopophos, Toposar, VePesid, VP156 | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| CytarabineAlso: Cytosar-U, Ara-C, Cytosine arabinoside | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
Primary outcome
To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML.
Time frame: Days 1-42 (all patients have to complete)
10 secondary outcomes
To determine the complete response rate (CR) for plerixafor when combined with MEC in patients with relapsed or refractory AML.
Time frame: Between days 15-42
To determine the safety and tolerability of plerixafor in combination with MEC
Time frame: Minimum of 30 days following completion of treatment
To determine the PK and explore potential PK drug-drug interactions between plerixafor and MEC.
Time frame: Predose, 15 min, 30 min , and 10 hrs
To determine the time to hematologic recovery
Time frame: For up to 2 years
To characterize the mobilization of leukemic cells with plerixafor plus G-CSF.
Time frame: Baseline, 6 hours
To characterize the effects of plerixafor plus G-CSF on SDF-1/CXCR4 signaling on leukemic blasts.
Time frame: Baseline, 6 hours
To determine the time to overall survival
Time frame: For up to 2 years
To determine the time to event-free survival
Time frame: For up to 2 years
To determine the time to duration of remission
Time frame: For up to 2 years
To determine the time to relapse-free survival
Time frame: For up to 2 years
Results and safety
The study was stopped early (reason given: Withdrawal of support from sponsor). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2015.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geoffrey Uy, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Plerixafor, Mitoxantrone and Etoposide in people with Leukemia, Myeloid, Acute, 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 9 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: stopped early, as of the sponsor's last update on 26 Jan 2015. 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 was stopped early (reason given: Withdrawal of support from sponsor). Results are not available in the source record.
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?
To determine the maximum tolerated dose and dose limiting toxicities of intravenous plerixafor when combined with MEC in patients with relapsed or refractory AML. (time frame: Days 1-42 (all patients have to complete)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Jan 2015.