Relapsed/Refractory AMLPhase 1NCT01319864
POETIC Plerixafor as a Chemosensitizing Agent for Relapsed Acute Leukemia and MDS in Pediatric Patients
A Phase 1 study testing Plerixafor Dose Escalation in people with Relapsed/Refractory AML and Relapsed/Refractory ALL, run by Seattle Children's Hospital at 9 sites in 2 countries.
Trial summary
In this Phase I study, we will test the safety of the drug plerixafor (MOBOZIL) at different dose levels, used together with other anti-cancer drugs-cytarabine and etoposide. We want to find out what effects, good and /or bad, this combination of drugs has on leukemia. Read more about this study
- Who is it for?
- Ages 3 to 29 years
- Conditions the study is for
- Relapsed/Refractory AML, Relapsed/Refractory ALL, Secondary AML/MDS
- What is being tested?
- Plerixafor Dose Escalation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Mar 2011to 28 Jun 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 3 to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- >= 3 years of age and <30 years old at study entry
- diagnosis of relapsed/refractory AML, ALL, secondary AML/MDS, or acute leukemia of ambiguous lineage and meet the following criteria:
- AML/MDS or leukemia with ambiguous lineage must have >5% blast in bone marrow
- ALL must have an M3 marrow
- ALL and AML must not have CNS disease
- patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy prior to entering study
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- Karnofsky score >50% for patients >16 years of age and Lansky >50% for patients <= 16 years of age
- adequate renal and hepatic function as defined in protocol
- adequate cardiac function as defined in protocol
Who cannot join
- ALL and AML patients with CNS disease
- Absolute blast count greater than 50,000/mcl
- Systemic fungal, bacterial, viral or other infection without improvement despite appropriate antibiotics or other treatment
- Significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance
- Patients who have second cancer, not including secondary AML
- Patients who are pregnant
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
Children's Healthcare of Atlanta/Emory University
Atlanta, Georgia, 30322
Johns Hopkins Medical Center
Baltimore, Maryland, 21231
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
The Children's Hospital of Denver
Denver, Colorado, 80045
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, 17033
The Children's Mercy Hospital and Clinics
Kansas City, Missouri, 64108
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Phoenix Children's Hospital
Phoenix, Arizona, 85016
About this study
Official title: A Phase I Study Using Plerixafor as a Chemosensitizing Agent for Relapsed Acute Leukemia and MDS in Pediatric Patients
In this Phase I study, we will test the safety of the drug plerixafor (MOBOZIL) at different dose levels, used together with other anti-cancer drugs-cytarabine and etoposide. We want to find out what effects, good and /or bad, this combination of drugs has on leukemia. Plerixafor is a drug that blocks a receptor on the leukemia cell, which prevents it from staying in the bone marrow where it can be resistant to chemotherapy. Plerixafor is FDA approved for mobilizing stem cells from the bone marrow in preparation for an autologous stem cell transplant. Cytarabine and etoposide have been used as part of standard chemotherapy for ALL and AML. However, the use of plerixafor with cytarabine and etoposide in pediatric patients with relapsed or refractory ALL, AML and MDS is considered experimental.
Read the detailed description
Approximately 500 children are diagnosed with AML every year, of whom around 60% are cured with current regimens based on anthracyclines and high dose cytarabine with or without stem cell transplant (SCT). Among the remaining 40% who are refractory or who relapse, outcome is dismal. Additionally, 20-30% of patients with childhood ALL relapse or become refractory to frontline therapies. The prognosis is poor in this patient population, particularly in patients with second or subsequent relapse and those who relapse following SCT. These patients present myriad challenges, as they usually have received a high cumulative anthracycline dose, and in the case of SCT, may have had significant organ toxicities and/or total body irradiation (TBI). Therefore, new therapeutic strategies need to be identified to enhance possible improved outcomes.
Recently, scientists have described a resistant, quiescent population of leukemia cells that have limitless self-renewal potential. The identification of these "leukemia stem cells" (LSCs) provides an additional strategy in treating and preventing relapsed/refractory acute leukemia. One mechanism for resistance to treatment is the protection afforded LSCs via the interaction between stem cell derived growth factor (CXCL-12/SDF-1α) and its receptor, CXCR4. These interactions are implicated in chemotaxis, homing, and survival/apoptosis of hematopoietic stem cells and progenitor cells. All AML and ALL cells express CXCR4 and SDF-1α. AMD3100 (plerixafor, MOBOZIL®) is a bicyclam that blocks CXCL-12 binding to and signaling through CXCR4, thus disrupting tumor-stroma interactions and mobilizing leukemia cells from their protective stromal environment. Plerixafor is currently FDA approved for use in stem cell mobilization for autologous transplantation in hematologic malignancies. Clinical trials in adult patients with relapsed AML have demonstrated promising results when combining plerixafor with cytotoxic chemotherapy.
This Phase I clinical trial will be the first to test the concept of a "chemosensitization" approach in children using Plerixafor. Patients aged 3 to 30 with relapsed/refractory AML, ALL or MDS will receive Plerixafor followed 4 hours later with combination chemotherapy consisting of etoposide and cytarabine daily for five days. We will determine the safety and tolerability of Plerixafor in combination with cytarabine and etoposide in pediatric and young adults with relapsed/refractory acute leukemias. The secondary objectives of this study will quantify the peripheral blood mobilization of blasts in response to Plerixafor using flow cytometry, measure initial CXCR4 expression on leukemic blasts and correlate with response, and determine the change in CXCR4 expression after protocol therapy. Finally, we will determine the pharmacokinetics of Plerixafor when administered with cytotoxic chemotherapy in this patient population.
- Conditions
- Relapsed/Refractory AML, Relapsed/Refractory ALL, Secondary AML/MDS, Acute Leukemia of Ambiguous Lineage, AML, ALL
- Being tested
- Plerixafor Dose Escalation
- Keywords
- leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence, Leukemia, Biphenotypic, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plerixafor Dose EscalationDrug
Also called AMD3100, MOBOZIL
Plerixafor dose escalation Dose Level -1 = 3 mg/m2/dose Dose Level 1 = 6 mg/m2/dose Dose Level 2 = 9 mg/m2/dose Dose Level 3 = 12 mg/m2/dose Dose Level 4 = 15 mg/m2/dose
Doses administered 4 hours prior to chemotherapy, then at the same approximate time of day on subsequent days, through the end of that cycle of chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Plerixafor, Dose Escalation | Experimental | Dose escalation of plerixafor administered intravenously in combination with IV cytarabine and IV etoposide in pediatric patients wtih relapsed/refractory AML/ALL. Receives: Drug: Plerixafor Dose Escalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Plerixafor given in combination with chemotherapy
To determine the safety and tolerability of plerixafor in combination with reinduction chemotherapy in pediatric and young adult patients with relapsed/refractory acute leukemia (AML/MDS and ALL)
Measured: 6 months post final enrollment
Secondary outcomes (7)
Response Rate
To estimate the response rate, within the context of a Phase I study, of Plerixafor given in sequential combination with cytarabine/etoposide (AE) in patients with relapsed or refractory ALL and AML/MDS.
Measured: 6 months post completion of treatment for final enrollment
Measure Peak Plasma Concentration (Cmax) of Plerixafor using serial peripheral blood sampling
Plasma pharmacokinetic parameters are estimated by noncompartmental analysis using PhoenixWinNonlin 7.0 (Certara) and are estimated from the observed concentration-time data.
Measured: 12 months following last sample collection
Leukemic blast mobilization
To measure peripheral blood mobilization of leukemic blasts by flow cytometry by comparing blood samples obtained before and after dose 1 of plerixafor, and to correlate degree of mobilization (expressed as % increase in circulating blasts) with response.
Measured: 12 months after final sample collection
CXCR4 expression on leukemic blasts
To measure the quantitative expression of CXCR4 on leukemic blasts at baseline and end of first course of treatment using flow cytometry and qRT-PCR, and correlate expression level with response.
Measured: 12 months after last patient completes therapy
Measure Area Under the Concentration-Time Curve (AUC) of Plerixafor using serial peripheral blood sampling
Plasma pharmacokinetic parameters are estimated by noncompartmental analysis using PhoenixWinNonlin 7.0 (Certara) and are estimated from the observed concentration-time data.
Measured: 12 months following last sample collection
Measure terminal half life (t1/2) of Plerixafor using serial peripheral blood sampling
Plasma pharmacokinetic parameters are estimated by noncompartmental analysis using PhoenixWinNonlin 7.0 (Certara) and are estimated from the observed concentration-time data.
Measured: 12 months following last sample collection
Measure systemic clearance of Plerixafor using serial peripheral blood sampling
Plasma pharmacokinetic parameters are estimated by noncompartmental analysis using PhoenixWinNonlin 7.0 (Certara) and are estimated from the observed concentration-time data.
Measured: 12 months following last sample collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2011 (estimated)
- Study startMar 2011
- Primary completion28 Jun 2013
- Study completion28 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory AMLStudies of the same condition, open and under way.
- More trials run by Seattle Children's HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Healthcare of Atlanta, The Pediatric Oncology Experimental Therapeutics Investigators' Consortium
- Responsible party
- Principal investigator, Todd Cooper, Seattle Children's Hospital
- Investigators
- Todd Cooper, DO, Principal investigator, Emory University/Children's Healthcare of Atlanta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01319864
- Sponsor's protocol ID
- IRB00047475
- Other IDs
- POETIC Plerixafor
- Status last verified
- Sep 2018
- First submitted
- 11 Mar 2011
- Last updated
- 7 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Using Plerixafor as a Chemosensitizing Agent for Relapsed Acute Leukemia and MDS in Pediatric Patients
- ClinicalTrials.gov ID
- NCT01319864
- Acronym / sponsor ID
- IRB00047475
- Conditions
- Relapsed/Refractory AML, Relapsed/Refractory ALL, Secondary AML/MDS, Acute Leukemia of Ambiguous Lineage, AML, ALL
- Keywords
- leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Seattle Children's HospitalUniversity, hospital or other
- Collaborators
- Children's Healthcare of Atlanta, The Pediatric Oncology Experimental Therapeutics Investigators' Consortium
- Study start
- Mar 2011
- Primary completion
- 28 Jun 2013 (actual)
- Study completion
- 28 Jun 2016 (actual)
- First posted
- 22 Mar 2011 (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 study, we will test the safety of the drug plerixafor (MOBOZIL) at different dose levels, used together with other anti-cancer drugs-cytarabine and etoposide. We want to find out what effects, good and /or bad, this combination of drugs has on leukemia. Plerixafor is a drug that blocks a receptor on the leukemia cell, which prevents it from staying in the bone marrow where it can be resistant to chemotherapy. Plerixafor is FDA approved for mobilizing stem cells from the bone marrow in preparation for an autologous stem cell transplant. Cytarabine and etoposide have been used as part of standard chemotherapy for ALL and AML. However, the use of plerixafor with cytarabine and etoposide in pediatric patients with relapsed or refractory ALL, AML and MDS is considered experimental.
Detailed description
Approximately 500 children are diagnosed with AML every year, of whom around 60% are cured with current regimens based on anthracyclines and high dose cytarabine with or without stem cell transplant (SCT). Among the remaining 40% who are refractory or who relapse, outcome is dismal. Additionally, 20-30% of patients with childhood ALL relapse or become refractory to frontline therapies. The prognosis is poor in this patient population, particularly in patients with second or subsequent relapse and those who relapse following SCT. These patients present myriad challenges, as they usually have received a high cumulative anthracycline dose, and in the case of SCT, may have had significant organ toxicities and/or total body irradiation (TBI). Therefore, new therapeutic strategies need to be identified to enhance possible improved outcomes.
Recently, scientists have described a resistant, quiescent population of leukemia cells that have limitless self-renewal potential. The identification of these "leukemia stem cells" (LSCs) provides an additional strategy in treating and preventing relapsed/refractory acute leukemia. One mechanism for resistance to treatment is the protection afforded LSCs via the interaction between stem cell derived growth factor (CXCL-12/SDF-1α) and its receptor, CXCR4. These interactions are implicated in chemotaxis, homing, and survival/apoptosis of hematopoietic stem cells and progenitor cells. All AML and ALL cells express CXCR4 and SDF-1α. AMD3100 (plerixafor, MOBOZIL®) is a bicyclam that blocks CXCL-12 binding to and signaling through CXCR4, thus disrupting tumor-stroma interactions and mobilizing leukemia cells from their protective stromal environment. Plerixafor is currently FDA approved for use in stem cell mobilization for autologous transplantation in hematologic malignancies. Clinical trials in adult patients with relapsed AML have demonstrated promising results when combining plerixafor with cytotoxic chemotherapy.
This Phase I clinical trial will be the first to test the concept of a "chemosensitization" approach in children using Plerixafor. Patients aged 3 to 30 with relapsed/refractory AML, ALL or MDS will receive Plerixafor followed 4 hours later with combination chemotherapy consisting of etoposide and cytarabine daily for five days. We will determine the safety and tolerability of Plerixafor in combination with cytarabine and etoposide in pediatric and young adults with relapsed/refractory acute leukemias. The secondary objectives of this study will quantify the peripheral blood mobilization of blasts in response to Plerixafor using flow cytometry, measure initial CXCR4 expression on leukemic blasts and correlate with response, and determine the change in CXCR4 expression after protocol therapy. Finally, we will determine the pharmacokinetics of Plerixafor when administered with cytotoxic chemotherapy in this patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Plerixafor, Dose Escalation | Experimental | Drug: Plerixafor Dose EscalationDose escalation of plerixafor administered intravenously in combination with IV cytarabine and IV etoposide in pediatric patients wtih relapsed/refractory AML/ALL. |
Who may qualify
- Ages
- 3 to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- >= 3 years of age and <30 years old at study entry
- diagnosis of relapsed/refractory AML, ALL, secondary AML/MDS, or acute leukemia of ambiguous lineage and meet the following criteria:
- AML/MDS or leukemia with ambiguous lineage must have >5% blast in bone marrow
- ALL must have an M3 marrow
- ALL and AML must not have CNS disease
Key exclusion criteria (6 listed)
- ALL and AML patients with CNS disease
- Absolute blast count greater than 50,000/mcl
- Systemic fungal, bacterial, viral or other infection without improvement despite appropriate antibiotics or other treatment
- Significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance
- Patients who have second cancer, not including secondary AML
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 |
|---|---|---|
| Plerixafor Dose EscalationAlso: AMD3100, MOBOZILPlerixafor dose escalation Dose Level -1 = 3 mg/m2/dose Dose Level 1 = 6 mg/m2/dose Dose Level 2 = 9 mg/m2/dose Dose Level 3 = 12 mg/m2/dose Dose Level 4 = 15 mg/m2/dose Doses administered 4 hours prior to chemotherapy, then at the same approximate time of day on subsequent days, through the end of that cycle of chemotherapy. | Drug | Plerixafor, Dose Escalation |
Primary outcome
Maximum Tolerated Dose (MTD) of Plerixafor given in combination with chemotherapy
Time frame: 6 months post final enrollment
To determine the safety and tolerability of plerixafor in combination with reinduction chemotherapy in pediatric and young adult patients with relapsed/refractory acute leukemia (AML/MDS and ALL)
7 secondary outcomes
Response Rate
Time frame: 6 months post completion of treatment for final enrollment
Measure Peak Plasma Concentration (Cmax) of Plerixafor using serial peripheral blood sampling
Time frame: 12 months following last sample collection
Leukemic blast mobilization
Time frame: 12 months after final sample collection
CXCR4 expression on leukemic blasts
Time frame: 12 months after last patient completes therapy
Measure Area Under the Concentration-Time Curve (AUC) of Plerixafor using serial peripheral blood sampling
Time frame: 12 months following last sample collection
Measure terminal half life (t1/2) of Plerixafor using serial peripheral blood sampling
Time frame: 12 months following last sample collection
Measure systemic clearance of Plerixafor using serial peripheral blood sampling
Time frame: 12 months following last sample collection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2018.
- clinical trials databaseLink 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.
Todd Cooper, DO principal investigator
Emory University/Children's Healthcare of Atlanta
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Plerixafor Dose Escalation in people with Relapsed/Refractory AML and Relapsed/Refractory ALL, run by Seattle Children's Hospital at 9 sites in 2 countries.
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 9 inclusion and 6 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 7 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada. 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?
Maximum Tolerated Dose (MTD) of Plerixafor given in combination with chemotherapy (time frame: 6 months post final enrollment). 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 7 Sep 2018.