Acute Myeloid LeukemiaNCT01141543
Feasibility and Efficiency Study of Leukemic Cell Mobilization With Plerixafor Injection
An observational study of Acute Myeloid Leukemia, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
The study will be conducted as a single center Phase I/II study to evaluate the safety of administering Plerixafor administered as part of a myeloablative preparative regimen (Institutional Protocol:Fludarabine 50mg/m2/da x 4 days, Busulfan 3.2mg/kg/day x 4 days, TBI 400cGy in divided fractions) for stem cell… Read more about this study
- Who is it for?
- Ages 18 to 61 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Plerixafor (mozobil)
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- May 2010to May 2014
- Phase
- Observational
- 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 61 years
- All sexes
- No healthy volunteers
- Adult
Study population: The study will be performed on patients undergoing myeloablative allogeneic stem cell transplants (PBSC or BM) from related or unrelated donors for the treatment of patients with AML in remission.
Who may be able to join
- Patients with AML in remission.
- Availability of a suitably matched related or unrelated donor
- Age 18-60 years
- Eligibility for a myeloablative transplant using the Institutional protocols R-FBT(400)-CSMF as preparative regimen for related donors and U-FBT(400)-CP(30)CS for unrelated donors.
- Eligible subjects who are illiterate will be offered participation in the study
Who cannot join
- Patients aged 61years or older
- Patients not eligible for the preparative regimens R-FBT(400)-CSMF or U-FBT(400)-CP(30)CS
- Pregnant or lactating females
- Creatinine of .>2x normal
- Bilirubin, AST, ALT > 2x normal
- MUGA of <50%
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients With AML Undergoing Allografting: Assessment of Feasibility and Efficacy
The study will be conducted as a single center Phase I/II study to evaluate the safety of administering Plerixafor administered as part of a myeloablative preparative regimen (Institutional Protocol:Fludarabine 50mg/m2/da x 4 days, Busulfan 3.2mg/kg/day x 4 days, TBI 400cGy in divided fractions) for stem cell transplant recipients with AML and to determine whether or not residual leukemic stem cells can be mobilized. Three patients will be enrolled into each of 4 sequential cohorts. Patients in the first cohort will receive 1 dose of Plerixafor (240mcg/kg sc) prior to administration of the first dose of Fludarabine and Busulfan. If tolerated it is planned to escalate the number of Plerixafor doses in the subsequent cohorts to 2. 3. and 4 to be administered before the respective 2nd, 3rd, and 4th dose of chemotherapy.
Read the detailed description
The study will be conducted as a single center Phase I/II study to evaluate the safety of administering PLERIXAFOR as part of a myeloablative preparative regimen (Institutional Protocol: FBT(400) - FLUDARABINE 50mg/m2/d x 4 days, BUSULFAN 3.2mg/kg/day x 4 days, TBI 400cGy in 2 fractions) for stem cell transplant recipients with Acute Myeloid Leukemia (AML) and to determine whether or not residual leukemic stem cells can be mobilized. Three patients will be enrolled into each of 4 sequential cohorts. Patients in the first cohort will receive 1 dose (240mcg/kg SC) of PLERIXAFOR ( MOZOBIL, formerly known as AMD3100) prior to administration of the first dose of FLUDARABINE and BUSULFAN It is planned to escalate the number of PLERIXAFOR doses in the subsequent cohorts to 2. 3. and 4 to be administered before the respective 2nd, 3rd, and 4th doses of chemotherapy. As primary endpoint the study will establish the toxicity of combined administration of PLERIXAFOR and the preparative regimen at each dose level. Secondary endpoints will include quantification of CXCR4 positive cells and candidates for leukemic disease propagating cells before and after administration of PLERIXAFOR. Mobilized cells will be examined for the ability to undergo apoptosis. Clinical parameters including SAE, OS and LFS are part of the evaluation.
The comparison of cell populations in peripheral blood before and after PLERIXAFOR may facilitate a better definition of minimal residual disease in patients deemed morphologically in a complete remission. The assessment after completion of the preparative regimen will provide a measurement of minimal residual disease prior to the transplant. The assessment of residual leukemic cells with respect to apoptosis will define their responsiveness to the administration of FLUDARABINE and BUSULFAN. The obtained information will facilitate development of a new platform to optimize preparation of patients for a transplant. Eg. Insufficient mobilization of leukemic cells may be addressed in future studies by combining mobilization strategies. Similarly, if cells are shown to be apoptosis resistant one may be able to include apoptosis inducing small molecules.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Plerixafor (mozobil)
- Keywords
- Plerixafor injection
- 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.
Plerixafor (mozobil)Drug
Also called Mozobil
Cohort 1: Administration of PLERIXAFOR (240mcg/kg sc) before the first dose of FLUDARABINE and BUSULFAN Cohort 2: Administration of PLERIXAFOR (240mcg/kg sc) before the first and second dose of FLUDARABINE and BUSULFAN.
Cohort 3: Administration of PLERIXAFOR (240mcg/kg sc) before the first, second, and third dose of FLUARABINE and BUSULFAN Cohort 4: Administration of PLERIXAFOR (240mcg/kg sc) before all four doses of FLUDARABINE and BUSULFAN
| Study group | Role | What they receive |
|---|---|---|
| cohort 1 | Patients in Cohort 1 will be followed with daily Flowcytometric studies to quantify CXCR4 positive cells.The samples will be obtained before the following doses of FLUDARABINE and BUSULFAN. Eighteen hrs (range 18 -20 hrs) after start of the last dose of FUDARABINE andBUSULFAN and before the first dose of TBI a PB sample as well as bone marrow aspirate and biopsy will be obtained to repeat the studies as conducted prior to the first dose of PLERIXAFOR Receives: Drug: Plerixafor (mozobil) | |
| Cohort 2 | Patients in Cohort 2 will receive the second dose of PLERIXAFOR 24 hrs after the first dose. A PB sample for a CBS and Flowcytometry will be drawn prior to the dose. Nine hrs later a further study sample for Flowcytometry will be obtained prior to administration of the second dose of FLUARABINE and BUSULFAN. Flowcytometric studies will be repeated on day 3 and 4. Eighteen hrs (range 18 - 20 hrs) after start of the last dose of FLUDARABINE and BUSULFAN and before the first dose of TBI a PB sample as well as bone marrow aspirate and biopsy will be obtained to repeat the studies as conducted prior to the first dose of PLERIXAFOR. Receives: Drug: Plerixafor (mozobil) | |
| cohort 3 | Cohort 3: Administration of PLERIXAFOR (240mcg/kg sc) before the first, second, and third dose of FLUARABINE and BUSULFAN Receives: Drug: Plerixafor (mozobil) | |
| Cohort 4 | Administration of PLERIXAFOR (240mcg/kg sc) before all four doses of FLUDARABINE and BUSULFAN Receives: Drug: Plerixafor (mozobil) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events as a measure of safety and tolerability using Plerixafor in conjunction with a myeloablative preparative regimen for a patients with AML undergoing an allogenic stem cell transplantation.
As primary endpoint the study is to establish whether or not the administration of Plerixafor during administration of a myeloablative preparative regimen for recipients of allografts can be tolerated.we will complete full protocol with a follow up period of 30 days for first patient than futher patients will be enrolled.Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be evaluated in the study.
Measured: one year
Secondary outcomes (6)
Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
Quantification of CXCR4 positive cells before and after administration of the first and subsequent doses of Plerixafor mesure andNumber of Participants with adverse Events as a measure of safety and tolerability.
Measured: one year
Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
Qutification of hypermethylation status of Mobilized cells and number of paticipants with adverse event as a measure of safety and Tolerability.
Measured: One Year
Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
Qutification of candidates for leukemic cell population s using a marker panel by flowcytometry.
Measured: one year
Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
Qutification of leukemic cells with suitable cytogenic or molrecular markerand number of participants with adverse events measure of safety and tolerability.
Measured: one year
Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be evaluated in the study.
Qutification of normal clonogenic hemopoietic progenitors and number of participants with adverse events as a measure of safety and tolerability.
Measured: one year
Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be evaluated in the study.
overall and Leukemia free survival at 1 year and number of Adverse events as a measure of safety and tolerability.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2010 (estimated)
- Study startMay 2010
- Primary completionApr 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Princess Margaret Hospital, Canada
- Responsible party
- Principal investigator, Dr. Hans Messner, University Health Network, Toronto
- Investigators
- Hans Messner, Ph.D, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01141543
- Sponsor's protocol ID
- 09-0756-C
- Status last verified
- Jul 2014
- First submitted
- 18 Mar 2010
- Last updated
- 18 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Michelis FV, Hedley DW, Malhotra S, Chow S, Loach D, Gupta V, Kim DD, Kuruvilla J, Lipton JH, Viswabandya A, Messner HA. Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients with Acute Myelogenous Leukemia Undergoing Allografting: Assessment of Safety and Tolerability. Biol Blood Marrow Transplant. 2019 Jun;25(6):1158-1163. doi: 10.1016/j.bbmt.2019.01.014. Epub 2019 Jan 14.
PubMed 30654137
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients With AML Undergoing Allografting: Assessment of Feasibility and Efficacy
- ClinicalTrials.gov ID
- NCT01141543
- Acronym / sponsor ID
- 09-0756-C
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Plerixafor injection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Princess Margaret Hospital, Canada
- Study start
- May 2010
- Primary completion
- Apr 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 10 Jun 2010 (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.
The study will be conducted as a single center Phase I/II study to evaluate the safety of administering Plerixafor administered as part of a myeloablative preparative regimen (Institutional Protocol:Fludarabine 50mg/m2/da x 4 days, Busulfan 3.2mg/kg/day x 4 days, TBI 400cGy in divided fractions) for stem cell transplant recipients with AML and to determine whether or not residual leukemic stem cells can be mobilized. Three patients will be enrolled into each of 4 sequential cohorts. Patients in the first cohort will receive 1 dose of Plerixafor (240mcg/kg sc) prior to administration of the first dose of Fludarabine and Busulfan. If tolerated it is planned to escalate the number of Plerixafor doses in the subsequent cohorts to 2. 3. and 4 to be administered before the respective 2nd, 3rd, and 4th dose of chemotherapy.
Detailed description
The study will be conducted as a single center Phase I/II study to evaluate the safety of administering PLERIXAFOR as part of a myeloablative preparative regimen (Institutional Protocol: FBT(400) - FLUDARABINE 50mg/m2/d x 4 days, BUSULFAN 3.2mg/kg/day x 4 days, TBI 400cGy in 2 fractions) for stem cell transplant recipients with Acute Myeloid Leukemia (AML) and to determine whether or not residual leukemic stem cells can be mobilized. Three patients will be enrolled into each of 4 sequential cohorts. Patients in the first cohort will receive 1 dose (240mcg/kg SC) of PLERIXAFOR ( MOZOBIL, formerly known as AMD3100) prior to administration of the first dose of FLUDARABINE and BUSULFAN It is planned to escalate the number of PLERIXAFOR doses in the subsequent cohorts to 2. 3. and 4 to be administered before the respective 2nd, 3rd, and 4th doses of chemotherapy. As primary endpoint the study will establish the toxicity of combined administration of PLERIXAFOR and the preparative regimen at each dose level. Secondary endpoints will include quantification of CXCR4 positive cells and candidates for leukemic disease propagating cells before and after administration of PLERIXAFOR. Mobilized cells will be examined for the ability to undergo apoptosis. Clinical parameters including SAE, OS and LFS are part of the evaluation.
The comparison of cell populations in peripheral blood before and after PLERIXAFOR may facilitate a better definition of minimal residual disease in patients deemed morphologically in a complete remission. The assessment after completion of the preparative regimen will provide a measurement of minimal residual disease prior to the transplant. The assessment of residual leukemic cells with respect to apoptosis will define their responsiveness to the administration of FLUDARABINE and BUSULFAN. The obtained information will facilitate development of a new platform to optimize preparation of patients for a transplant. Eg. Insufficient mobilization of leukemic cells may be addressed in future studies by combining mobilization strategies. Similarly, if cells are shown to be apoptosis resistant one may be able to include apoptosis inducing small molecules.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| cohort 1 | – | Drug: Plerixafor (mozobil)Patients in Cohort 1 will be followed with daily Flowcytometric studies to quantify CXCR4 positive cells.The samples will be obtained before the following doses of FLUDARABINE and BUSULFAN. Eighteen hrs (range 18 -20 hrs) after start of the last dose of FUDARABINE andBUSULFAN and before the first dose of TBI a PB sample as well as bone marrow aspirate and biopsy will be obtained to repeat the studies as conducted prior to the first dose of PLERIXAFOR |
| Cohort 2 | – | Drug: Plerixafor (mozobil)Patients in Cohort 2 will receive the second dose of PLERIXAFOR 24 hrs after the first dose. A PB sample for a CBS and Flowcytometry will be drawn prior to the dose. Nine hrs later a further study sample for Flowcytometry will be obtained prior to administration of the second dose of FLUARABINE and BUSULFAN. Flowcytometric studies will be repeated on day 3 and 4. Eighteen hrs (range 18 - 20 hrs) after start of the last dose of FLUDARABINE and BUSULFAN and before the first dose of TBI a PB sample as well as bone marrow aspirate and biopsy will be obtained to repeat the studies as conducted prior to the first dose of PLERIXAFOR. |
| cohort 3 | – | Drug: Plerixafor (mozobil)Cohort 3: Administration of PLERIXAFOR (240mcg/kg sc) before the first, second, and third dose of FLUARABINE and BUSULFAN |
| Cohort 4 | – | Drug: Plerixafor (mozobil)Administration of PLERIXAFOR (240mcg/kg sc) before all four doses of FLUDARABINE and BUSULFAN |
Who may qualify
- Ages
- 18 to 61 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The study will be performed on patients undergoing myeloablative allogeneic stem cell transplants (PBSC or BM) from related or unrelated donors for the treatment of patients with AML in remission.
Key inclusion criteria (5 listed)
- Patients with AML in remission.
- Availability of a suitably matched related or unrelated donor
- Age 18-60 years
- Eligibility for a myeloablative transplant using the Institutional protocols R-FBT(400)-CSMF as preparative regimen for related donors and U-FBT(400)-CP(30)CS for unrelated donors.
- Eligible subjects who are illiterate will be offered participation in the study
Key exclusion criteria (6 listed)
- Patients aged 61years or older
- Patients not eligible for the preparative regimens R-FBT(400)-CSMF or U-FBT(400)-CP(30)CS
- Pregnant or lactating females
- Creatinine of .>2x normal
- Bilirubin, AST, ALT > 2x normal
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 (mozobil)Also: MozobilCohort 1: Administration of PLERIXAFOR (240mcg/kg sc) before the first dose of FLUDARABINE and BUSULFAN Cohort 2: Administration of PLERIXAFOR (240mcg/kg sc) before the first and second dose of FLUDARABINE and BUSULFAN. Cohort 3: Administration of PLERIXAFOR (240mcg/kg sc) before the first, second, and third dose of FLUARABINE and BUSULFAN Cohort 4: Administration of PLERIXAFOR (240mcg/kg sc) before all four doses of FLUDARABINE and BUSULFAN | Drug | Cohort 2, Cohort 4, cohort 1, cohort 3 |
Primary outcome
Adverse events as a measure of safety and tolerability using Plerixafor in conjunction with a myeloablative preparative regimen for a patients with AML undergoing an allogenic stem cell transplantation.
Time frame: one year
As primary endpoint the study is to establish whether or not the administration of Plerixafor during administration of a myeloablative preparative regimen for recipients of allografts can be tolerated.we will complete full protocol with a follow up period of 30 days for first patient than futher patients will be enrolled.Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be evaluated in the study.
6 secondary outcomes
Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
Time frame: one year
Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
Time frame: One Year
Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
Time frame: one year
Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
Time frame: one year
Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be evaluated in the study.
Time frame: one year
Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be evaluated in the study.
Time frame: one year
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 18 Jul 2014.
- Derived from this study: PubMed 30654137Michelis FV, Hedley DW, Malhotra S, Chow S, Loach D, Gupta V, Kim DD, Kuruvilla J, Lipton JH, Viswabandya A, Messner HA. Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients with Acute Myelogenous Leukemia Undergoing Allografting: Assessment of Safety and Tolerability. Biol Blood Marrow Transplant. 2019 Jun;25(6):1158-1163. doi: 10.1016/j.bbmt.2019.01.014. Epub 2019 Jan 14.
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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.
Hans Messner, Ph.D principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Myeloid Leukemia, run by University Health Network, Toronto at 1 site in Canada.
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 5 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 18 Jul 2014. 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 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.
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?
Adverse events as a measure of safety and tolerability using Plerixafor in conjunction with a myeloablative preparative regimen for a patients with AML undergoing an allogenic stem cell transplantation. (time frame: one year). 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 NCT01141543, 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 18 Jul 2014.