Leukemia, Myeloid, AcutePhase 1/2AMD3100+MECNCT00512252

AMD3100 Plus Mitoxantrone, Etoposide and Cytarabine in Acute Myeloid Leukemia

A Phase 1/2 study testing AMD3100, Mitoxantrone and Etoposide in people with Leukemia, Myeloid, Acute, 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

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Trial summary

This study is a phase I/II study to determine the safety and efficacy of AMD3100 when combined with mitoxantrone, etoposide, and cytarabine in patients with relapsed or refractory AML. 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?: AMD3100, Mitoxantrone and Etoposide
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 52 participants
Where: 1 siteUnited States
Study dates: Jul 2007to Jun 2010
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 by WHO criteria with one of the following:
Primary refractory disease following >= 1 rounds of induction chemotherapy
First relapse or higher
Age between 18 and 70 years of age
Adequate organ function defined as Creatinine <= 1.5 x institutional ULN; AST, ALT, total bilirubin <= 2 x ULN; Left ventricular ejection fraction of >= 40% by MUGA scan
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 > 20 x 103 /mm3
Active CNS involvement with leukemia
Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
Pregnant or nursing
Receiving any other investigational agent

Show all 9Show fewer

Colony stimulating factors filgrastim, pegfilgrastim or sargramostim within 2 weeks of study
Less than 2 weeks from the completion of any previous cytotoxic chemotherapy
Severe concurrent illness that would limit compliance with study requirements

Trial locations and contacts

1 site in 1 country.

United States1 site

Washington University
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML

This study is a phase I/II study to determine the safety and efficacy of AMD3100 when combined with mitoxantrone, etoposide, and cytarabine in patients with relapsed or refractory AML.

We hypothesize that disrupting the interaction between AML blasts and the marrow microenvironment with AMD3100 may enhance the cytotoxic effect of chemotherapy.

Read the detailed description

The interaction of leukemic blasts with the bone marrow microenvironment is postulated to be an important mediator of chemoresistance in AML. Although a number of receptor / ligand pairs have been implicated, the CXCR4 / SDF-1 axis functions as the principal regulator of homing and retention of both normal and malignant hematopoietic cells in the marrow. AMD3100 is a bicyclam molecule which reversibly blocks CXCR4 binding to SDF-1 and is being developed clinically as a mobilization agent for hematopoietic stem cell transplantation. Preclinical data from our group has demonstrated that in murine models, plerixafor can disrupt the interaction of leukemic cells with the marrow microenvironment and sensitize blasts to the effect of chemotherapy. Based on these data, we have initiated a phase I/II study in patients with relapsed or refractory AML in which plerixafor is administered prior to salvage chemotherapy.

Conditions: Leukemia, Myeloid, Acute
Being tested: AMD3100, Mitoxantrone, Etoposide, Cytarabine
Keywords: Plerixafor, CXCR4, Chemosensitization
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.

AMD3100Drug
Also called Plerixafor
MitoxantroneDrug
Also called Novantrone
EtoposideDrug
Also called VP-16, Vepesid, Etopophos
CytarabineDrug
Also called Ara-C, Cytosar-U, Tarabine PFS

Study groups in NCT00512252
Study group	Role	What they receive
Phase I Dose Escalation	Experimental	* AMD3100 SQ on days 0-5 * Mitoxantrone on days 1-5 * Etoposide on days 1-5 * Cytarabine on days 1-5 Dose Level 1 AMD3100 dose = 80 mcg/kg/d Dose Level 2 AMD3100 dose = 160 mcg/kg/d Receives: Drug: AMD3100; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine
Phase II Dose Treatment	Experimental	* AMD 3100 SQ on days 0-5 * Mitoxantrone on days 1-5 * Etoposide on days 1-5 * Cytarabine on days 1-5 Dose Level 3 AMD3100 dose=240 mcg/kg/d (this was the Phase II dose) Receives: Drug: AMD3100; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

What is being measured

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

Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML
A standard 3+3 design was used in the Phase I portion starting with the AMD3100 dose of 80 mcg/kg and escalating by 80 mcg/kg for each successive cohort up to a maximum of 240 mcg/kg/d. The optimal dose was defined as the highest dose of AMD3100 <= 240 mcg/kg at which 0-1 of 6 patients experienced a dose limiting toxicity.
Measured: Completion of all patients in Phase I portion (232 days)
Phase II Only: Complete Response Rate of AMD3100 + MEC
Responses were assessed according to the International Working Group Criteria for AML. All patients who received at least one dose of AMD3100 were considered evaluable for response.
Response rate was the rate of complete remission plus complete remission with incomplete blood count recovery (CR + CRi).
Measured: 42 days
Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions
Measured: 42 days

Secondary outcomes (10)

Safety and Tolerability of AMD3100 + MEC.
Treatment related mortality (deaths occurring during treatment)
Measured: 42 days
Time to Neutrophil Recovery
Defined as the date of the first dose of AMD3100 to the date that the absolute neutrophil count >1,000 cells/mm^3.
Measured: 42 days
Time to Platelet Recovery
Defined as the date of the first dose of AMD3100 to the date that the platelet count is >100,000/mm3 in the absence of platelet transfusions.
Measured: 42 days
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I)
Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0.
Characterization of the mobilized cells as well as the kinetics of mobilization will be determined by analyzing the surface expression of mobilized cells by flow cytometry at the specified time points in conjunction with their total leukocyte count from the patient's CBC.
Measured: Day 0
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I)
Measured at 0 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 24 hours after AMD3100 dose on Day 0.
Measured: Day 0
Pharmacokinetics of AMD3100 on MEC
Measured: Day 1 - Phase 2 only
Time to Progression
Measured: Every 6 months
Treatment Failure
Treatment failures includes those patients for whom treatment has failed to achieve a CR or a CRi.
Measured: 42 days
Overall Survival
Measured: 1 year
Relapse-free Survival
This is determined only for patients achieving a complete remission. Defined as the interval from the date of the first documentation of a leukemia free state to date of recurrence or death due to any cause.
Kaplain-Meier estimate was used.
Measured: 1 year

Timeline

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

Jul 2007Jun 2010

First posted7 Aug 2007 (estimated)
Study startJul 2007
Primary completionJun 2010
Study completionJun 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 52 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00512252
Sponsor's protocol ID: 07-0227 / 201011796
Acronym: AMD3100+MEC
Status last verified: Oct 2016
First submitted: 6 Aug 2007
Last updated: 12 Dec 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Uy GL, Rettig MP, Motabi IH, McFarland K, Trinkaus KM, Hladnik LM, Kulkarni S, Abboud CN, Cashen AF, Stockerl-Goldstein KE, Vij R, Westervelt P, DiPersio JF. A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood. 2012 Apr 26;119(17):3917-24. doi: 10.1182/blood-2011-10-383406. Epub 2012 Feb 2.
PubMed 22308295

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Leukemia, Myeloid, Acute trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Study of AMD3100 With Mitoxantrone, Etoposide and Cytarabine (AMD3100+MEC) in Relapsed or Refractory AML
ClinicalTrials.gov ID: NCT00512252
Acronym / sponsor ID: AMD3100+MEC / 07-0227 / 201011796
Conditions: Leukemia, Myeloid, Acute
Keywords: Plerixafor, CXCR4, Chemosensitization
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 52 participants (actual)
Lead sponsor: Washington University School of MedicineUniversity, hospital or other
Study start: Jul 2007
Primary completion: Jun 2010 (actual)
Study completion: Jun 2010 (actual)
First posted: 7 Aug 2007 (estimated)
Results: Posted 22 Sep 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is a phase I/II study to determine the safety and efficacy of AMD3100 when combined with mitoxantrone, etoposide, and cytarabine in patients with relapsed or refractory AML.

We hypothesize that disrupting the interaction between AML blasts and the marrow microenvironment with AMD3100 may enhance the cytotoxic effect of chemotherapy.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Phase I Dose Escalation	Experimental	Drug: AMD3100, Drug: Mitoxantrone, Drug: Etoposide, Drug: Cytarabine* AMD3100 SQ on days 0-5 * Mitoxantrone on days 1-5 * Etoposide on days 1-5 * Cytarabine on days 1-5 Dose Level 1 AMD3100 dose = 80 mcg/kg/d Dose Level 2 AMD3100 dose = 160 mcg/kg/d
Phase II Dose Treatment	Experimental	Drug: AMD3100, Drug: Mitoxantrone, Drug: Etoposide, Drug: Cytarabine* AMD 3100 SQ on days 0-5 * Mitoxantrone on days 1-5 * Etoposide on days 1-5 * Cytarabine on days 1-5 Dose Level 3 AMD3100 dose=240 mcg/kg/d (this was the Phase II dose)

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Acute myeloid leukemia diagnosed by WHO criteria with one of the following:
Age between 18 and 70 years of age
Adequate organ function defined as Creatinine <= 1.5 x institutional ULN; AST, ALT, total bilirubin <= 2 x ULN; Left ventricular ejection fraction of >= 40% by MUGA scan
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

Key exclusion criteria (9 listed)

Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants)
Peripheral blood blast count > 20 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
AMD3100Also: Plerixafor	Drug	Phase I Dose Escalation, Phase II Dose Treatment
MitoxantroneAlso: Novantrone	Drug	Phase I Dose Escalation, Phase II Dose Treatment
EtoposideAlso: VP-16, Vepesid, Etopophos	Drug	Phase I Dose Escalation, Phase II Dose Treatment
CytarabineAlso: Ara-C, Cytosar-U, Tarabine PFS	Drug	Phase I Dose Escalation, Phase II Dose Treatment

Primary outcome

Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML
Time frame: Completion of all patients in Phase I portion (232 days)
A standard 3+3 design was used in the Phase I portion starting with the AMD3100 dose of 80 mcg/kg and escalating by 80 mcg/kg for each successive cohort up to a maximum of 240 mcg/kg/d. The optimal dose was defined as the highest dose of AMD3100 <= 240 mcg/kg at which 0-1 of 6 patients experienced a dose limiting toxicity.
Phase II Only: Complete Response Rate of AMD3100 + MEC
Time frame: 42 days
Responses were assessed according to the International Working Group Criteria for AML. All patients who received at least one dose of AMD3100 were considered evaluable for response. Response rate was the rate of complete remission plus complete remission with incomplete blood count recovery (CR + CRi).
Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions
Time frame: 42 days

10 secondary outcomes

Safety and Tolerability of AMD3100 + MEC.
Time frame: 42 days
Time to Neutrophil Recovery
Time frame: 42 days
Time to Platelet Recovery
Time frame: 42 days
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of Total Leukocytes (Phase I)
Time frame: Day 0
Characterize the Mobilization of Leukemic Cells With AMD3100 by Measuring the Peak Mobilization of AML Blasts (Phase I)
Time frame: Day 0
Pharmacokinetics of AMD3100 on MEC
Time frame: Day 1 - Phase 2 only
Time to Progression
Time frame: Every 6 months
Treatment Failure
Time frame: 42 days
Overall Survival
Time frame: 1 year
Relapse-free Survival
Time frame: 1 year

Results and safety

Results posted to the registry on 22 Sep 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I Dose Escalation (Dose Level 1)	3	3
Phase I Dose Escalation (Dose Level 2)	3	3
Phase II Dose Treatment (Dose Level 3)	46	43

Primary outcome: Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML

Time frame: Completion of all patients in Phase I portion (232 days). Number. Unit: mcg/kg

Measure	Phase I Dose Escalation n = 12
Value	240

Population analysed: The Phase I Dose Escalation portion included (3) patients enrolled in Dose Level 1 and (3) patients enrolled in Dose Level 2. The (6) patients enrolled in Dose Level 3 that determined the Phase II dose are included in the population for this outcome.

Primary outcome: Phase II Only: Complete Response Rate of AMD3100 + MEC

Time frame: 42 days. Number. Unit: percentage of participants

Measure	First Relapse, First Salvage n = 32	Primary Refractory n = 10	>= Second Relapse/Salvage n = 4	Total n = 46
CR + CRi	56	20	25	46
CR only	47	20	25	39

Primary outcome: Ability of AMD3100 + MEC to Induce dsDNA Damage and Apoptosis in Leukemic Blasts From Bone Marrow or Peripheral Blood Fractions

Time frame: 42 days

Population analysed: This outcome was not analyzed as data was not collected.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event assessment was collected from start of treatment for 42 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I Dose Escalation (Dose Level 1)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Phase I Dose Escalation (Dose Level 2)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Phase II Dose Treatment (Dose Level 3)	3 of 46 (6.5%)	46 of 46 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22308295Uy GL, Rettig MP, Motabi IH, McFarland K, Trinkaus KM, Hladnik LM, Kulkarni S, Abboud CN, Cashen AF, Stockerl-Goldstein KE, Vij R, Westervelt P, DiPersio JF. A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood. 2012 Apr 26;119(17):3917-24. doi: 10.1182/blood-2011-10-383406. Epub 2012 Feb 2.
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 L. Uy, MD 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 1/2 study testing AMD3100, 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 7 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: finished, as of the sponsor's last update on 12 Dec 2016. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Phase I Only: Optimal Dose of AMD3100 Plus MEC in Patients With Relapsed or Refractory AML (time frame: Completion of all patients in Phase I portion (232 days)). The study lists 3 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 NCT00512252, which also lists 1 linked publication.

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 12 Dec 2016.