Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant

NCT01280955 | Completed Phase 1 Results DMC

• 1 other identifier: Pro00024433
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Failure of Bone Marrow Graft

Keywords

Plerixafor and Allogeneic Myeloablative Stem Cell Transplant

Outcome Measures

Primary Outcomes (3)

• Time to Neutrophil Recovery

  leukocytes \> 500/ul on 2 consecutive days

  100 Days post Transplant

• Time to Platelet Recovery

  platelet \> 20,000/ul on 2 consecutive days

  100 Days Post Transplant

• Plerixafor-associated Adverse Events

  100 Days Post Transplant

Secondary Outcomes (25)

• Transplant-related Mortality

  100 Days Post Transplant

• Absolute Lymphocyte Count at Day 90

  90 days

• IL-12 at Day 30

  30 days

• Participants Experiencing Grade II-IV Acute Graft Versus Host Disease

  100 days

• CD3+ Cell Count at Day 90

  90 Days

Study Arms (1)

Transplant Recipients

EXPERIMENTAL

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

Interventions

Plerixafor DRUG

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.

Also known as: AMD3100, Mozobil

Transplant Recipients

Eligibility Criteria

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

You may qualify if:

• Age 18 to 65 years.
• /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.

You may not qualify if:

• Patients with \> 5% blasts in bone marrow or peripheral circulation.
• Uncontrolled infection.
• Class III or IV angina as per NYHA criteria.

Sponsors & Collaborators

• Mitchell Horwitz, MD: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (2)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Green MM, Chao N, Chhabra S, Corbet K, Gasparetto C, Horwitz A, Li Z, Venkata JK, Long G, Mims A, Rizzieri D, Sarantopoulos S, Stuart R, Sung AD, Sullivan KM, Costa L, Horwitz M, Kang Y. Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery. J Hematol Oncol. 2016 Aug 17;9(1):71. doi: 10.1186/s13045-016-0301-2.

  PMID: 27535663 DERIVED

MeSH Terms

Interventions

plerixafor

Limitations and Caveats

Study was limited to recipients of matched adult donor grafts

Results Point of Contact

• Title: Mitchell Horwitz, MD
• Organization: Duke University Medical Center

mitchel.horwitz@duke.edu

919-668-1045

Study Officials

• Mitchell Horwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Saurabh Chhabra, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assoc Professor of Medicine

Study Record Dates

• First Submitted: January 20, 2011
• First Posted: January 21, 2011
• Study Start: December 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: May 1, 2015
• Last Updated: April 25, 2017
• Results First Posted: November 26, 2015

Record last verified: 2017-03

Locations

US (2)