search
Back to results

A Phase II Study Evaluating the Safety and Efficacy of Subcutaneous Plerixafor

Primary Purpose

Related Donors Donating Peripheral Blood Stem Cells (PBSC) to a Family Member, Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Plerixafor
Sponsored by
Center for International Blood and Marrow Transplant Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Related Donors Donating Peripheral Blood Stem Cells (PBSC) to a Family Member

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Donor:

  • Donor eligibility will be determined according to applicable federal, state and local regulations and institutional standards
  • 18-65 years of age
  • 6/6 HLA-matched sibling
  • Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor
  • Serum creatinine <2.0mg/dl

Recipient:

  • 18 to 65 years of age
  • 6/6 HLA antigen matched sibling willing to donate PBSC for transplant
  • Fulfill individual Transplant Center Criteria for transplant

  • One of the following diagnoses:

    • Acute myelogenous leukemia (AML) in 1st remission or beyond with <5% marrow blasts and no circulating blasts. Marrow must be done within 30 days of the start of transplant conditioning regimen in alignment with other pre-transplant assessments.
    • Acute lymphoblastic leukemia (ALL) in 1st remission or beyond with <5% marrow blasts and no circulating blasts
    • Myelodysplastic syndrome, either intermediate-1,2, or high risk by International Prognostic Scoring System or transfusion dependent
    • Chronic myelogenous leukemia (CML) failing or intolerant to tyrosine kinase inhibitor based therapy
    • Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or in relapse (but with at least stable disease after most recent therapy)
    • Chronic lymphocytic leukemia (CLL), relapsing after at least one prior regimen, or in remission with 17p deletion
  • Serum creatinine must be <2.0mg/dl
  • Total bilirubin and AST <3x normal
  • Infectious disease marker (IDM) monitoring will be performed per institutional standards
  • Karnofsky performance status of 70% or greater.
  • Patients who have undergone a prior autologous transplantation are eligible for a reduced intensity transplant only

Exclusion Criteria:

Donor:

  • Donor unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
  • Donor already enrolled on another investigational agent study
  • Pregnant or breast feeding females, or females not willing or able to use adequate contraception if sexually active

Recipient:

  • Patient unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
  • Patients with active, uncontrolled infection at the time of the transplant preparative regimen
  • Pregnant or breast feeding females, or females not willing or able to use adequate contraception if sexually active
  • Patients with a history of previous CNS tumor involvement showing active symptoms or signs along with documented disease on lumbar puncture and MRI of the brain within 30 days of start of conditioning
  • A condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of primary and secondary endpoints.

Sites / Locations

  • H. Lee Moffitt Cancer Center
  • Emory University
  • University of Chicago
  • Massachusetts General Hospital
  • University of Minnesota
  • Mayo Clinic
  • Washington University
  • Duke University
  • Cleveland Clinic
  • Ohio State University
  • West Virginia University
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

No Intervention

Arm Label

Related donors receiving plerixafor

Recipients, myeloablative regimen

Recipients, reduced intensity conditioning regimen.

Arm Description

Collection of sufficient CD34+ cells using plerixafor as the mobilizing agent. Eligible donors determined according to institutional standards 18-65 years of age 6/6 HLA-matched sibling Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor Serum creatinine <1.5 x institution upper limit of normal (ULN) or estimated creatinine clearance (CLCR) >50 mL/min Treatment Description: Receive subcutaneous plerixafor at 240 μg/kg and commence leukapheresis approximately 4 hours later. Leukapheresis will be performed up to two consecutive days. The target CD34+ cell dose is > 4.0 x 106/kg with a minimum of > 2.0 x 106/kg.

Patients undergoing conditioning under a myeloablative regimen Myeloablative (one of four general regimens): Busulfan (> 9 mg/kg po or iv total) with fludarabine Busulfan (> 9 mg/kg po or iv total) with cyclophosphamide Total body irradiation (> 1000 cGy) plus etoposide Total body irradiation (> 500 cGy) plus cyclophosphamide

Patients undergoing conditioning using a reduced intensity conditioning regimen. Reduced Intensity (one of three general regimens): Busulfan (< 9 mg/kg po or iv total) plus fludarabine Melphalan (100-140 mg/m2 iv total) plus fludarabine Fludarabine plus cyclophosphamide (> 2000 mg/m2 total)

Outcomes

Primary Outcome Measures

Percentage of Donors Whose Cells Were Successfully Mobilized and Collected With a Sufficient CD34+ Cell Dose Using Plerixafor as the Mobilizing Agent, Using an Intention-to-treat Analysis.
Donor mobilization following plerixafor was considered successful if ≥ 2.0x106 CD34+ cells/kg recipient weight was collected in no more than two leukapheresis collections.

Secondary Outcome Measures

Incidence and Severity of Acute Toxicities
Incidence and severity of acute toxicities before and during apheresis experienced by donors receiving plerixafor. Acute toxicities are graded according to the NCI Common Terminology Criteria for Adverse Events, version 4.0. This outcome measure is descriptive. Grade of maximum toxicity across all time points is reported. Higher grades denote worse outcomes. 0 = None, 1 = Mild, 2 = Moderate, 3 = severe.
Adverse Effects
Adverse effects experienced by donors receiving plerixafor up to one year post donation. Number of participants with a maximum MTC >0 reported at each individual time point. Adverse effects are graded according to the NCI Common Terminology Criteria for Adverse Events, version 4.0. This outcome measure is descriptive. Participants can experience adverse effects at more than one time point evaluated. Higher grades denote worse outcomes. 0 = None, 1 = Mild, 2 = Moderate, 3 = severe.
Incidence of and Kinetics of Neutrophil and Platelet Recovery After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
Incidence of and kinetics of neutrophil and platelet recovery by day 100 in recipients after transplantation of hematopoietic cells mobilized with plerixafor.
T-cell (CD3+) and Myeloid (CD33+) Chimerism After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
T-cell (CD3+) and myeloid (CD33+) chimerism in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.
Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
Incidence of primary graft failure in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.
Incidence of Acute Graft-versus-host Disease (GVHD)
Incidence of acute graft-versus-host disease (GVHD) in recipients after transplantation of hematopoietic cells mobilized with plerixafor
Immune Reconstitution
Rate and quality of immune reconstitution as evidenced by peripheral blood immunophenotype after transplantation of hematopoietic cells mobilized with plerixafor.
Incidence of Cytomegalovirus (CMV) Reactivation After Transplantation With Cells Mobilized With Plerixafor.
Percentage of recipients with prior CMV infection whose CMV was reactivated after transplantation with cell mobilized with plerixafor
Treatment-related Mortality and Disease Relapse/Progression
Incidence of treatment-related mortality and disease relapse/progression in recipients after transplantation of hematopoietic cells mobilized with plerixafor
Progression-free and Overall Survival
Probability of progression-free and overall survival after transplantation of hematopoietic cells mobilized with plerixafor
Cellular Composition of Allografts
Cellular composition of allografts mobilized with plerixafor (stem/progenitor cells, T/B/ (Natural killer) NK-cells)
Incidence of Chronic Graft-versus-host Disease (GVHD)
Incidence of chronic graft-versus-host disease (GVHD) in recipients after transplantation of hematopoietic cells mobilized with plerixafor
Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
Incidence of secondary graft failure in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.
CD34+ Cell Count of Allografts
CD34+ cell count of allografts mobilized with plerixafor

Full Information

First Posted
September 24, 2012
Last Updated
September 8, 2023
Sponsor
Center for International Blood and Marrow Transplant Research
Collaborators
Genzyme, a Sanofi Company, Sanofi
search

1. Study Identification

Unique Protocol Identification Number
NCT01696461
Brief Title
A Phase II Study Evaluating the Safety and Efficacy of Subcutaneous Plerixafor
Official Title
A Phase II Study Evaluating the Safety and Efficacy of Subcutaneous Plerixafor for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Recipients With Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Center for International Blood and Marrow Transplant Research
Collaborators
Genzyme, a Sanofi Company, Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase II, open-label, two strata, multicenter, prospective study of plerixafor-mobilized HLA-identical sibling allografts in recipients with hematological malignancies. This study will establish the safety and efficacy of subcutaneous plerixafor for this purpose.
Detailed Description
The primary objective is to determine the proportion of donors whose cells can be successfully mobilized and collected with a sufficient CD34+ cell dose using plerixafor as the mobilizing agent, using an intention-to-treat analysis. Donor mobilization following plerixafor will be considered successful if ≥ 2.0x10e6 CD34+ cells/kg recipient weight are collected in no more than two leukapheresis collections. All donors receiving plerixafor will be included in the analysis of the primary objective based on the intention-to-treat principle.Recipients will be classified into one of the two strata, myeloablative or reduced intensity, according to his/her conditioning regimen. The target enrollment is 64 donor/recipient pairs, 32 pairs per stratum.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Related Donors Donating Peripheral Blood Stem Cells (PBSC) to a Family Member, Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Chronic Myelogenous Leukemia, Non-Hodgkin's Lymphoma, Hodgkin's Disease, Chronic Lymphocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
127 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Related donors receiving plerixafor
Arm Type
Experimental
Arm Description
Collection of sufficient CD34+ cells using plerixafor as the mobilizing agent. Eligible donors determined according to institutional standards 18-65 years of age 6/6 HLA-matched sibling Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor Serum creatinine <1.5 x institution upper limit of normal (ULN) or estimated creatinine clearance (CLCR) >50 mL/min Treatment Description: Receive subcutaneous plerixafor at 240 μg/kg and commence leukapheresis approximately 4 hours later. Leukapheresis will be performed up to two consecutive days. The target CD34+ cell dose is > 4.0 x 106/kg with a minimum of > 2.0 x 106/kg.
Arm Title
Recipients, myeloablative regimen
Arm Type
No Intervention
Arm Description
Patients undergoing conditioning under a myeloablative regimen Myeloablative (one of four general regimens): Busulfan (> 9 mg/kg po or iv total) with fludarabine Busulfan (> 9 mg/kg po or iv total) with cyclophosphamide Total body irradiation (> 1000 cGy) plus etoposide Total body irradiation (> 500 cGy) plus cyclophosphamide
Arm Title
Recipients, reduced intensity conditioning regimen.
Arm Type
No Intervention
Arm Description
Patients undergoing conditioning using a reduced intensity conditioning regimen. Reduced Intensity (one of three general regimens): Busulfan (< 9 mg/kg po or iv total) plus fludarabine Melphalan (100-140 mg/m2 iv total) plus fludarabine Fludarabine plus cyclophosphamide (> 2000 mg/m2 total)
Intervention Type
Drug
Intervention Name(s)
Plerixafor
Other Intervention Name(s)
Mozobil, AMD3000
Primary Outcome Measure Information:
Title
Percentage of Donors Whose Cells Were Successfully Mobilized and Collected With a Sufficient CD34+ Cell Dose Using Plerixafor as the Mobilizing Agent, Using an Intention-to-treat Analysis.
Description
Donor mobilization following plerixafor was considered successful if ≥ 2.0x106 CD34+ cells/kg recipient weight was collected in no more than two leukapheresis collections.
Time Frame
donation
Secondary Outcome Measure Information:
Title
Incidence and Severity of Acute Toxicities
Description
Incidence and severity of acute toxicities before and during apheresis experienced by donors receiving plerixafor. Acute toxicities are graded according to the NCI Common Terminology Criteria for Adverse Events, version 4.0. This outcome measure is descriptive. Grade of maximum toxicity across all time points is reported. Higher grades denote worse outcomes. 0 = None, 1 = Mild, 2 = Moderate, 3 = severe.
Time Frame
baseline, Day 1, Day 2, Day 3
Title
Adverse Effects
Description
Adverse effects experienced by donors receiving plerixafor up to one year post donation. Number of participants with a maximum MTC >0 reported at each individual time point. Adverse effects are graded according to the NCI Common Terminology Criteria for Adverse Events, version 4.0. This outcome measure is descriptive. Participants can experience adverse effects at more than one time point evaluated. Higher grades denote worse outcomes. 0 = None, 1 = Mild, 2 = Moderate, 3 = severe.
Time Frame
30 minutes, 60 minutes, 120 minutes, 240 minutes, 1 month, 6 months, 12 months post donation for each subject
Title
Incidence of and Kinetics of Neutrophil and Platelet Recovery After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
Description
Incidence of and kinetics of neutrophil and platelet recovery by day 100 in recipients after transplantation of hematopoietic cells mobilized with plerixafor.
Time Frame
Day +1 through neutrophil recovery or Day 21 (whichever is first)
Title
T-cell (CD3+) and Myeloid (CD33+) Chimerism After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
Description
T-cell (CD3+) and myeloid (CD33+) chimerism in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.
Time Frame
Chimerism was evaluated at serial timepoints post HCT in patients in both RIC and MAC strata. Chimerism was assessed at Day +28, +100, +180, and +365
Title
Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
Description
Incidence of primary graft failure in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.
Time Frame
Day 28
Title
Incidence of Acute Graft-versus-host Disease (GVHD)
Description
Incidence of acute graft-versus-host disease (GVHD) in recipients after transplantation of hematopoietic cells mobilized with plerixafor
Time Frame
Day 100
Title
Immune Reconstitution
Description
Rate and quality of immune reconstitution as evidenced by peripheral blood immunophenotype after transplantation of hematopoietic cells mobilized with plerixafor.
Time Frame
Day 28, 100, 180, 365
Title
Incidence of Cytomegalovirus (CMV) Reactivation After Transplantation With Cells Mobilized With Plerixafor.
Description
Percentage of recipients with prior CMV infection whose CMV was reactivated after transplantation with cell mobilized with plerixafor
Time Frame
day 365
Title
Treatment-related Mortality and Disease Relapse/Progression
Description
Incidence of treatment-related mortality and disease relapse/progression in recipients after transplantation of hematopoietic cells mobilized with plerixafor
Time Frame
Day 180, 365
Title
Progression-free and Overall Survival
Description
Probability of progression-free and overall survival after transplantation of hematopoietic cells mobilized with plerixafor
Time Frame
Day 180, 365
Title
Cellular Composition of Allografts
Description
Cellular composition of allografts mobilized with plerixafor (stem/progenitor cells, T/B/ (Natural killer) NK-cells)
Time Frame
donation
Title
Incidence of Chronic Graft-versus-host Disease (GVHD)
Description
Incidence of chronic graft-versus-host disease (GVHD) in recipients after transplantation of hematopoietic cells mobilized with plerixafor
Time Frame
Day 365
Title
Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
Description
Incidence of secondary graft failure in recipients after transplantation of hematopoietic cells mobilized with plerixafor. This outcome measure is descriptive.
Time Frame
Day 365
Title
CD34+ Cell Count of Allografts
Description
CD34+ cell count of allografts mobilized with plerixafor
Time Frame
donation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Donor: Donor eligibility will be determined according to applicable federal, state and local regulations and institutional standards 18-65 years of age 6/6 HLA-matched sibling Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor Serum creatinine <2.0mg/dl Recipient: 18 to 65 years of age 6/6 HLA antigen matched sibling willing to donate PBSC for transplant Fulfill individual Transplant Center Criteria for transplant One of the following diagnoses: Acute myelogenous leukemia (AML) in 1st remission or beyond with <5% marrow blasts and no circulating blasts. Marrow must be done within 30 days of the start of transplant conditioning regimen in alignment with other pre-transplant assessments. Acute lymphoblastic leukemia (ALL) in 1st remission or beyond with <5% marrow blasts and no circulating blasts Myelodysplastic syndrome, either intermediate-1,2, or high risk by International Prognostic Scoring System or transfusion dependent Chronic myelogenous leukemia (CML) failing or intolerant to tyrosine kinase inhibitor based therapy Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or in relapse (but with at least stable disease after most recent therapy) Chronic lymphocytic leukemia (CLL), relapsing after at least one prior regimen, or in remission with 17p deletion Serum creatinine must be <2.0mg/dl Total bilirubin and aspartate aminotransferase (AST) <3x normal Infectious disease marker (IDM) monitoring will be performed per institutional standards Karnofsky performance status of 70% or greater. Patients who have undergone a prior autologous transplantation are eligible for a reduced intensity transplant only Exclusion Criteria: Donor: Donor unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing Donor already enrolled on another investigational agent study Pregnant or breast feeding females, or females not willing or able to use adequate contraception if sexually active Recipient: Patient unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing Patients with active, uncontrolled infection at the time of the transplant preparative regimen Pregnant or breast feeding females, or females not willing or able to use adequate contraception if sexually active Patients with a history of previous central nervous system (CNS) tumor involvement showing active symptoms or signs along with documented disease on lumbar puncture and MRI of the brain within 30 days of start of conditioning A condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of primary and secondary endpoints.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steve Devine, MD
Organizational Affiliation
NMDP/BeTheMatch
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30890544
Citation
Chen YB, Le-Rademacher J, Brazauskas R, Kiefer DM, Hamadani M, DiPersio JF, Litzow MR, Craig M, Horwitz ME, Artz AS, McClune BL, Fernandez HF, Duong HK, Kobusingye H, Proue M, Drexler RJ, Horowitz MM, Shaw BE, Miller JP, Hosoba S, Waller EK, Devine SM. Plerixafor alone for the mobilization and transplantation of HLA-matched sibling donor hematopoietic stem cells. Blood Adv. 2019 Mar 26;3(6):875-883. doi: 10.1182/bloodadvances.2018027599.
Results Reference
derived

Learn more about this trial

A Phase II Study Evaluating the Safety and Efficacy of Subcutaneous Plerixafor

We'll reach out to this number within 24 hrs