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

Phase 2

Completed

Conditions: Related Donors Donating Peripheral Blood Stem Cells (PBSC) to a Family Member
Myelodysplastic Syndrome
Hodgkin's Disease
Chronic Lymphocytic Leukemia
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Chronic Myelogenous Leukemia
Non-Hodgkin's Lymphoma

Interventions: Drug: Plerixafor

Registration Number: NCT01696461

Lead Sponsor: Center for International Blood and Marrow Transplant Research

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 127

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Related donors receiving plerixafor	Plerixafor	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.

Primary Outcome Measures

Name	Time	Method
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.	donation	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

Name	Time	Method
Incidence and Severity of Acute Toxicities	baseline, Day 1, Day 2, Day 3	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	30 minutes, 60 minutes, 120 minutes, 240 minutes, 1 month, 6 months, 12 months post donation for each subject	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	Day +1 through neutrophil recovery or Day 21 (whichever is first)	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	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	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	Day 28	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)	Day 100	Incidence of acute graft-versus-host disease (GVHD) in recipients after transplantation of hematopoietic cells mobilized with plerixafor
Immune Reconstitution	Day 28, 100, 180, 365	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.	day 365	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	Day 180, 365	Incidence of treatment-related mortality and disease relapse/progression in recipients after transplantation of hematopoietic cells mobilized with plerixafor
Progression-free and Overall Survival	Day 180, 365	Probability of progression-free and overall survival after transplantation of hematopoietic cells mobilized with plerixafor
Cellular Composition of Allografts	donation	Cellular composition of allografts mobilized with plerixafor (stem/progenitor cells, T/B/ (Natural killer) NK-cells)
Incidence of Chronic Graft-versus-host Disease (GVHD)	Day 365	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	Day 365	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	donation	CD34+ cell count of allografts mobilized with plerixafor

Trial Locations

Locations (12): H. Lee Moffitt Cancer Center
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Tampa, Florida, United States
Emory University
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Atlanta, Georgia, United States
Ohio State University
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Columbus, Ohio, United States
University of Chicago
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Chicago, Illinois, United States
West Virginia University
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Morgantown, West Virginia, United States
Washington University
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Saint Louis, Missouri, United States
Medical College of Wisconsin
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Milwaukee, Wisconsin, United States
Massachusetts General Hospital
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Boston, Massachusetts, United States
Duke University
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Durham, North Carolina, United States
Cleveland Clinic
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Cleveland, Ohio, United States
Mayo Clinic
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Rochester, Minnesota, United States
University of Minnesota
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Minneapolis, Minnesota, United States