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Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Mitchell Horwitz, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01280955
First received: January 20, 2011
Last updated: March 24, 2017
Last verified: March 2017
  Purpose
This phase I/II clinical trial will test the safety and the efficacy of post transplant administration of plerixafor in enhancing hematological recovery in humans. Patients who are appropriate candidates for myeloablative allogeneic stem cell transplantation from an HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for enrollment. The investigators plan to enroll a total of 50 patients for this study (30 patients with HLA-matched sibling or matched unrelated donor transplant, and 20 patients with umbilical cord blood transplant). During phase I study, a small number of patients (3-6 patients from each group) will be enrolled to determine the safety of post transplant administration of plerixafor. Patients will receive plerixafor given at 240 µg/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment. Limiting toxicities are defined as primary or secondary graft failure, plerixafor-related severe premature ventricular arrhythmia or death. If safety criteria are met from the investigators phase I study, the investigators will proceed with phase II study to determine the efficacy of post transplant administration of plerixafor in enhancing haematological recovery. The experimental aspect of this study is the use of plerixafor and all other aspects of care will be in line with the standard of care. Both Phase I and Phase II patients will be combined for efficacy analysis, and data collected from this study will be compared with the investigators historical control. The results from this study will set the stage and provide the justification for a larger phase 3 trial.

Condition Intervention Phase
Failure of Bone Marrow Graft Drug: Plerixafor Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study: Enhancing Donor Hematopoietic Cell Engraftment With Plerixafor in Myeloablative Allogeneic Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Mitchell Horwitz, MD, Duke University Medical Center:

Primary Outcome Measures:
  • Time to Neutrophil Recovery [ Time Frame: 100 Days post Transplant ]
    leukocytes > 500/ul on 2 consecutive days

  • Time to Platelet Recovery [ Time Frame: 100 Days Post Transplant ]
    platelet > 20,000/ul on 2 consecutive days

  • Plerixafor-associated Adverse Events [ Time Frame: 100 Days Post Transplant ]

Secondary Outcome Measures:
  • Transplant-related Mortality [ Time Frame: 100 Days Post Transplant ]
  • Absolute Lymphocyte Count at Day 90 [ Time Frame: 90 days ]
    Cell reconstitution - absolute lymphocyte count at day 90 post transplant.

  • IL-12 at Day 30 [ Time Frame: 30 days ]
    IL-12 at day 30; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.

  • Participants Experiencing Grade II-IV Acute Graft Versus Host Disease [ Time Frame: 100 days ]
    We are reporting on the number of participants experiencing a grade II-IV acute graft versus host disease will be assessed weekly through Day 100 post transplant. Staging and grading of Acute GvHD is graded by pattern of organ involvement and clinical performance status using the Grading Index of Acute GvHD (Gluckman) and the Grading Index of Acute GVHD by the CIBMTR (Centers for International Blood and Marrow Transplant Research)

  • CD3+ Cell Count at Day 90 [ Time Frame: 90 Days ]
    Cell reconstitution - CD3+ cell count at day 90 post transplant. This is a marker for the function of your immune system.

  • CD4 Cell Count at Day 90 [ Time Frame: 90 days ]
    CD4 cell count at Day 90; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.

  • CD8 Cell Count at Day 90 [ Time Frame: 90 days ]
    CD8 cell count at Day 90; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).

  • NK Cell Count at Day 90 [ Time Frame: 90 days ]
    NK cell count at Day 90;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.

  • B Cell Count at Day 90 [ Time Frame: 90 days ]
    B cell count at Day 90; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.

  • IFN Gamma at Day 30 [ Time Frame: 30 days ]
    IFN gamma at day 30; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.

  • TNF-alpha at Day 30 [ Time Frame: 30 days ]
    TNF-alpha at day 30; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.

  • CD4 Cell Count at Day 30 [ Time Frame: 30 days ]
    CD4 cell count at Day 30; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.

  • CD4 Cell Count at Day 60 [ Time Frame: 60 days ]
    CD4 cell count at Day 60; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.

  • CD8 Cell Count at Day 30 [ Time Frame: 30 days ]
    CD8 cell count at Day 30; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).

  • CD8 Cell Count at Day 60 [ Time Frame: 60 days ]
    CD8 cell count at Day 60; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).

  • NK Cell Count at Day 30 [ Time Frame: 30 days ]
    NK cell count at Day 30;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.

  • NK Cell Count at Day 60 [ Time Frame: 60 days ]
    NK cell count at Day 60;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.

  • B Cell Count at Day 30 [ Time Frame: 30 days ]
    B cell count at Day 30; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.

  • B Cell Count at Day 60 [ Time Frame: 60 days ]
    B cell count at Day 60; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.

  • IL-12 at Day 7 [ Time Frame: 7 days ]
    IL-12 at day 7; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.

  • IL-12 at Day 14 [ Time Frame: 14 days ]
    IL-12 at day 14; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.

  • IFN Gamma at Day 7 [ Time Frame: 7 days ]
    IFN gamma at day 7; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.

  • IFN Gamma at Day 14 [ Time Frame: 14 days ]
    IFN gamma at day 14; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.

  • TNF-alpha at Day 7 [ Time Frame: 7 days ]
    TNF-alpha at day 7; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.

  • TNF-alpha at Day 14 [ Time Frame: 14 days ]
    TNF-alpha at day 14; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.


Enrollment: 41
Actual Study Start Date: December 2011
Study Completion Date: May 2015
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transplant Recipients
Transplant recipients from matched sibling donors and dual cord donors. Subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Drug: Plerixafor
Matched sibling or Dual Cord donor subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Other Names:
  • AMD3100
  • Mozobil

Detailed Description:
Recruitment to this trial will be stratified by donor type as HLA (human leukocyte antigen) matched sibling, matched unrelated donor or umbilical cord blood. Patients will be conditioned with a myeloablative regimen such as, but not limited to, total body irradiation and cyclophosphamide. The donor stem cell grafts will come from mobilized peripheral blood of 8/8 or 7/8 HLA-identical family members, 8/8 (HLA A, B, C, DRBeta1) allele-level matched unrelated donors, or dual umbilical cord blood grafts with at least 4 of 6 HLA matching at HLA A and B (low resolution) and DRBeta1 (at high resolution). The target CD34+ cell dose will be 5 X 10(6)/kg recipient ideal body weight. For HLA matched sibling or matched unrelated donor (MUD) transplants, all patients will receive a minimum of 2 X 10(6) CD 24+ cells/kg. For cord blood transplants, each unit will contain a minimum total nucleated cell count of of 1.5 X 10(7)/kg. Post-transplant GVHD (graft versus host disease) prophylaxis will be given per institutional standard.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 to 65 years.
  • 8/8 or 7/8 HLA-identical matched sibling OR Allele level 8/8 (HLA-A, B, C, DR Beta1)matched unrelated donor or 4/6 or better HLA matched cord blood.
  • Patients with high risk hematologic malignancies who are appropriate candidates for a myeloablative allogeneic stem cell transplantation.
  • Patients with a history of CNS disease must have been treated and have no active CNS disease at the time of protocol treatment.
  • ECOG performance status < or equal to 2
  • Patients must have adequate function of other organ systems as measured by:
  • Creatinine clearance (by Cockcroft Gault equation) > or equal to 30ml/min. Hepatic transaminases (ALT/AST) < or equal to 4 x normal, bilirubin < or equal to 2.0 mg/dl.
  • Pulmonary function tests demonstrating FVC and FEV1 of > or equal to 50% of predicted for age and DLCO > or equal to 50% of predicted.
  • Ejection fraction of > or equal to 45% by echocardiogram, radionuclide scan or cardiac MRI.
  • Patients must be HIV negative.
  • Patients must not be pregnant.

Exclusion Criteria:

  • Patients with > 5% blasts in bone marrow or peripheral circulation.
  • Uncontrolled infection.
  • Class III or IV angina as per NYHA criteria.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01280955

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Mitchell Horwitz, MD
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Mitchell Horwitz, MD Duke University
Principal Investigator: Saurabh Chhabra, MD Medical University of South Carolina
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mitchell Horwitz, MD, Assoc Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01280955     History of Changes
Other Study ID Numbers: Pro00024433
Study First Received: January 20, 2011
Results First Received: September 27, 2015
Last Updated: March 24, 2017

Keywords provided by Mitchell Horwitz, MD, Duke University Medical Center:
Plerixafor and Allogeneic Myeloablative Stem Cell Transplant

Additional relevant MeSH terms:
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 22, 2017