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

Sponsor

Center for International Blood and Marrow Transplant Research (Other)

Overall Status

Completed

CT.gov ID

NCT01696461

Collaborator

Genzyme, a Sanofi Company (Industry), Sanofi (Industry)

128

Enrollment

Locations

Arm

Duration (Months)

10.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Related Donors Donating 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	Drug: Plerixafor	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

128 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

May 1, 2013

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Related donors receiving plerixafor Collection of sufficient CD34+ cells using plerixafor as the mobilizing agent.	Drug: Plerixafor Other Names: Mozobil AMD3000

Arm

Intervention/Treatment

Experimental: Related donors receiving plerixafor

Collection of sufficient CD34+ cells using plerixafor as the mobilizing agent.

Drug: Plerixafor

Other Names:

Mozobil

AMD3000

Outcome Measures

Primary Outcome Measures

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 [donation]
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 ≥ 2.0x106 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.

Secondary Outcome Measures

incidence and severity of acute toxicities before and during apheresis experienced by donors receiving plerixafor [baseline, donation]
To ascertain the incidence and severity of acute toxicities before and during apheresis experienced by donors receiving plerixafor
Characterize the adverse effects experienced by donors receiving plerixafor up to one year post donation [baseline, donation, 1 week, 1 month, 6 months, 1 year]
To characterize the adverse effects experienced by donors receiving plerixafor up to one year post donation
The incidence of and kinetics of neutrophil and platelet recovery after transplantation of hematopoietic cells mobilized with plerixafor [Day 21, 28, 56, 100, 180, 270, 365]
To determine the incidence of and kinetics of neutrophil and platelet recovery after transplantation of hematopoietic cells mobilized with plerixafor
Description of T-cell (CD3+) and myeloid (CD33+) chimerism after transplantation of hematopoietic cells mobilized with plerixafor [Day 28, 100, 180, 365]
To describe T-cell (CD3+) and myeloid (CD33+) chimerism after transplantation of hematopoietic cells mobilized with plerixafor
Incidence of primary and secondary graft failure after transplantation of hematopoietic cells mobilized with plerixafor [Day 21, 28, 56, 100, 180, 270, 365]
To determine the incidence of primary and secondary graft failure after transplantation of hematopoietic cells mobilized with plerixafor
Incidence of acute and chronic graft-versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with plerixafor [Day 21, 28, 56, 100, 180, 270, 365]
To determine the incidence of acute and chronic graft-versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with plerixafor
Rate and quality of immune reconstitution as evidenced by peripheral blood immunophenotype after transplantation of hematopoietic cells mobilized with plerixafor [Day 28, 100, 180, 365]
To assess the rate and quality of immune reconstitution as evidenced by peripheral blood immunophenotype after transplantation of hematopoietic cells mobilized with plerixafor
incidence of CMV reactivation after transplantation of hematopoietic cells mobilized with plerixafor in CMV seropositive recipients [Day 100, 180, 365]
To determine the incidence of CMV reactivation after transplantation of hematopoietic cells mobilized with plerixafor in CMV seropositive recipients
incidence of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with plerixafor [Day 21, 28, 56, 100, 180, 270, 365]
To determine the incidence of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with plerixafor
probability of progression-free and overall survival after transplantation of hematopoietic cells mobilized with plerixafor [Day 21, 28, 56, 100, 180, 270, 365]
To determine the probability of progression-free and overall survival after transplantation of hematopoietic cells mobilized with plerixafor
describe the cellular composition of allografts mobilized with plerixafor (stem/progenitor cells, T/B/NK-cells) [donation]
To describe the cellular composition of allografts mobilized with plerixafor (stem/progenitor cells, T/B/NK-cells)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country
1	H. Lee Moffitt Cancer Center	Tampa	Florida	United States
2	Emory University	Atlanta	Georgia	United States
3	University of Chicago	Chicago	Illinois	United States
4	Massachusetts General Hospital	Boston	Massachusetts	United States
5	University of Minnesota	Minneapolis	Minnesota	United States
6	Mayo Clinic	Rochester	Minnesota	United States
7	Washington University	Saint Louis	Missouri	United States
8	Duke University	Durham	North Carolina	United States
9	Cleveland Clinic	Cleveland	Ohio	United States
10	Ohio State University	Columbus	Ohio	United States
11	West Virginia University	Morgantown	West Virginia	United States
12	Medical College of Wisconsin	Milwaukee	Wisconsin	United States