Clinical trial NCT01141543: Feasibility and Efficiency Study of Leukemic Cell Mobilization With Plerixafor Injection
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Myeloid Leukemia
Keywords: Plerixafor injection
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Princess Margaret Hospital, Canada
First posted: 2010-06-10
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 61
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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.

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.

Eligibility criteria: 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%

Primary outcomes:
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.
timeFrame: one year
Secondary outcomes:
measure: Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
timeFrame: one year
measure: Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
timeFrame: One Year
measure: Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
timeFrame: one year
measure: Quantification of leukemic progenitor cells after administration of Plerixafor as a myeloablative preparative regimen for a patient with AML undergoing a stem cell transplantation.
timeFrame: one year
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be evaluated in the study.
timeFrame: one year
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability will be evaluated in the study.
timeFrame: one year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Hans Messner, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.