Feasibility and Efficiency Study of Leukemic Cell Mobilization With Plerixafor Injection

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01141543
• Other study ID #: 09-0756-C
• Status: Completed
• Phase: N/A
• First received: March 18, 2010
• Last updated: July 16, 2014
• Start date: May 2010
• Est. completion date: May 2014

Study information

• Verified date: July 2014
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Observational

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 61 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion criteria:

• 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%

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Plerixafor (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

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Princess Margaret Hospital, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	one year	No
Secondary	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.	one year	No
Secondary	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.	One Year	No
Secondary	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.	one year	No
Secondary	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.	one year	No
Secondary	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.	one year	No
Secondary	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.	one year	No