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

NCT01696461 | Completed Phase 2 Results DMC

• 1 other identifier: 09-PLEX
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 12

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  donation

Secondary Outcomes (14)

• Incidence and Severity of Acute Toxicities

  baseline, Day 1, Day 2, Day 3

• Adverse Effects

  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

  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

  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

  Day 28

Study Arms (3)

Related donors receiving plerixafor

EXPERIMENTAL

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.

Drug: Plerixafor

Recipients, myeloablative regimen

NO INTERVENTION

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

Recipients, reduced intensity conditioning regimen.

NO INTERVENTION

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)

Interventions

Plerixafor DRUG

Also known as: Mozobil, AMD3000

Related donors receiving plerixafor

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Donor:
• Donor eligibility will be determined according to applicable federal, state and local regulations and institutional standards
• years of age
• /6 HLA-matched sibling
• Fulfill individual Transplant Center criteria to serve as a mobilized blood cell donor
• Serum creatinine \<2.0mg/dl
• Recipient:
• to 65 years of age
• /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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Center for International Blood and Marrow Transplant Research: lead
• Genzyme, a Sanofi Company: collaborator
• Sanofi: collaborator

Study Sites (12)

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Location

Emory University

Atlanta, Georgia, United States

Location

University of Chicago

Chicago, Illinois, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, United States

Location

University of Minnesota

Minneapolis, Minnesota, United States

Location

Mayo Clinic

Rochester, Minnesota, United States

Location

Washington University

St Louis, Missouri, United States

Location

Duke University

Durham, North Carolina, United States

Location

Cleveland Clinic

Cleveland, Ohio, United States

Location

Ohio State University

Columbus, Ohio, United States

Location

West Virginia University

Morgantown, West Virginia, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Location

Related Publications (1)

• 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.

  PMID: 30890544 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Leukemia, B-Cell

Limitations and Caveats

Although this was a prospective multicenter trial, conclusions are limited by the single arm design and small sample size.

Results Point of Contact

• Title: Dr. Steven Devine
• Organization: National Marrow Donor Program/BeTheMatch

sdevine2@nmdp.org

7634068239

Study Officials

• Steve Devine, MD

  NMDP/BeTheMatch

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2012
• First Posted: October 1, 2012
• Study Start: May 1, 2013
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: September 14, 2023
• Results First Posted: September 14, 2023

Record last verified: 2023-05

Locations

US (12)