Clinical trial NCT01696461: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Center for International Blood and Marrow Transplant Research
Sponsor class: NETWORK
Collaborators: name: Genzyme, a Sanofi Company
name: Sanofi
First posted: 2012-10-01
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: donation
Secondary outcomes:
measure: Incidence and Severity of Acute Toxicities
timeFrame: baseline, Day 1, Day 2, Day 3
measure: Adverse Effects
timeFrame: 30 minutes, 60 minutes, 120 minutes, 240 minutes, 1 month, 6 months, 12 months post donation for each subject
measure: Incidence of and Kinetics of Neutrophil and Platelet Recovery After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
timeFrame: Day +1 through neutrophil recovery or Day 21 (whichever is first)
measure: T-cell (CD3+) and Myeloid (CD33+) Chimerism After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
timeFrame: 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
measure: Primary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
timeFrame: Day 28
measure: Incidence of Acute Graft-versus-host Disease (GVHD)
timeFrame: Day 100
measure: Immune Reconstitution
timeFrame: Day 28, 100, 180, 365
measure: Incidence of Cytomegalovirus (CMV) Reactivation After Transplantation With Cells Mobilized With Plerixafor.
timeFrame: day 365
measure: Treatment-related Mortality and Disease Relapse/Progression
timeFrame: Day 180, 365
measure: Progression-free and Overall Survival
timeFrame: Day 180, 365
measure: Cellular Composition of Allografts
timeFrame: donation
measure: Incidence of Chronic Graft-versus-host Disease (GVHD)
timeFrame: Day 365
measure: Secondary Graft Failure After Transplantation of Hematopoietic Cells Mobilized With Plerixafor
timeFrame: Day 365
measure: CD34+ Cell Count of Allografts
timeFrame: donation
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: NMDP/BeTheMatch
name: Steve Devine, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.