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

Center for International Blood and Marrow Transplant Research127 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

127

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (12)

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Duke University

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

...and 2 more locations

Outcomes

Primary Outcomes

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.

Time frame: donation

Secondary Outcomes

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.

Time frame: baseline, Day 1, Day 2, Day 3

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.

Time frame: 30 minutes, 60 minutes, 120 minutes, 240 minutes, 1 month, 6 months, 12 months post donation for each subject

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.

Time frame: Day +1 through neutrophil recovery or Day 21 (whichever is first)

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.

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

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.

Time frame: Day 28

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

Time frame: Day 100

Immune Reconstitution

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

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

Time frame: day 365

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

Time frame: Day 180, 365

Progression-free and Overall Survival

Probability of progression-free and overall survival after transplantation of hematopoietic cells mobilized with plerixafor

Time frame: Day 180, 365

Cellular Composition of Allografts

Cellular composition of allografts mobilized with plerixafor (stem/progenitor cells, T/B/ (Natural killer) NK-cells)

Time frame: donation

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

Time frame: Day 365

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.

Time frame: Day 365

CD34+ Cell Count of Allografts

CD34+ cell count of allografts mobilized with plerixafor

Time frame: donation

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

Overview

Conditions

Interventions

Eligibility

Locations (12)

Outcomes

Primary Outcomes

Secondary Outcomes