Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant

NCT ID: NCT01280955

Last Updated: 2017-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2015-05-31

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.

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.

Conditions

Failure of Bone Marrow Graft

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

Plerixafor

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

AMD3100; Mozobil

Eligibility 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.

• 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

Mitchell Horwitz, MD

OTHER

Sponsor Role: lead

Responsible Party

Mitchell Horwitz, MD

Assoc Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mitchell Horwitz, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Saurabh Chhabra, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Duke University Medical Center

Durham, North Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27535663 (View on PubMed)

Other Identifiers

Pro00024433

Identifier Type: -

Identifier Source: org_study_id