Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant

This study is currently recruiting participants.
Verified November 2013 by Duke University
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Mitchell Horwitz, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01280955
First received: January 20, 2011
Last updated: November 6, 2013
Last verified: November 2013
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Duke University:

Primary Outcome Measures:
  • Time to neutrophil recovery [ Time Frame: 100 Days post Transplant ] [ Designated as safety issue: Yes ]
    leukocytes > 500/ul on 2 consecutive days

  • Time to platelet recovery [ Time Frame: 100 Days Post Transplant ] [ Designated as safety issue: Yes ]
    platelet > 20,000/ul on 2 consecutive days

  • Plerixafor-associated adverse events [ Time Frame: 100 Days Post Transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival at day +100 [ Time Frame: 100 Days Post Transplant ] [ Designated as safety issue: Yes ]
  • Immunological reconstitution [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    As determined by CD4 count, CD8 count, NK cells, B cells and Immunloglobulin level on day +30, 60+, and +90

  • Plasma cytokines/chemokines [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    As determined by IL-12, IFN-gamma, TNF-alpha and macrophage inhibitory protein-1 measured at day +7, +14 and +30.

  • Incidence of grade II/IV acute graft versus host disease [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    Weekly through Day 100 post transplant


Estimated Enrollment: 50
Study Start Date: December 2011
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Matched sibling or Dual Cord Donor
This arm will be stratified into transplant recipients from 30 matched sibling donors and 20 dual cord blood donors.
Drug: Plerixafor
Patients 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 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 prophylaxis will be given per institutional standard.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01280955

Contacts
Contact: Krista Rowe, RN MS AOCNS 919-684-7115 krista.rowe@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27705
Contact: Mitchell Horwitz, MD    919-668-1012    horwi001@mc.duke.edu   
Contact: Krista Rowe, RN    919-684-7115    krista.rowe@duke.edu   
Sub-Investigator: Nelson Chao, MD         
Principal Investigator: Mitchell Horwitz, MD         
Sub-Investigator: David Rizzieri, MD         
Sub-Investigator: Gwynn Long, MD         
Sub-Investigator: Cristina Gasparetto, MD         
Sub-Investigator: Keith Sullivan, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Yubin Kang, MD    843-792-4271    kangy@musc.edu   
Contact: Jessica Simons, CHES, CCRP    843-792-8856    simonsjl@musc.edu   
Principal Investigator: Yubin Kang, MD         
Sponsors and Collaborators
Mitchell Horwitz
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Mitchell Horwitz, MD Duke University
Principal Investigator: Yubin Kang, MD Medical University of South Carolina
  More Information

No publications provided

Responsible Party: Mitchell Horwitz, 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
Last Updated: November 6, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
Plerixafor and Allogeneic Myeloablative Stem Cell Transplant

Additional relevant MeSH terms:
JM 3100
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014