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

NCT ID: NCT01696461

Last Updated: 2023-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2016-08-31

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Related donors receiving 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.

Group Type: EXPERIMENTAL

Plerixafor

Intervention Type: DRUG

Recipients, myeloablative regimen

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Recipients, reduced intensity conditioning regimen.

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)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Plerixafor

Intervention Type: DRUG

Other Intervention Names

Mozobil; AMD3000

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Center for International Blood and Marrow Transplant Research

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steve Devine, MD

Role: PRINCIPAL_INVESTIGATOR

NMDP/BeTheMatch

Locations

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

West Virginia University

Morgantown, West Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30890544 (View on PubMed)

Other Identifiers

09-PLEX

Identifier Type: -

Identifier Source: org_study_id