Overview

This trial is active, not recruiting.

Condition failure of bone marrow graft
Treatment plerixafor
Phase phase 1/phase 2
Sponsor Mitchell Horwitz, MD
Collaborator Genzyme, a Sanofi Company
Start date December 2011
End date September 2014
Trial size 43 participants
Trial identifier NCT01280955, Pro00024433

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
This arm will be stratified into transplant recipients from 30 matched sibling donors and 20 dual cord blood 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.
plerixafor AMD3100
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.

Primary Outcomes

Measure
Time to Neutrophil Recovery
time frame: 100 Days post Transplant
Time to Platelet Recovery
time frame: 100 Days Post Transplant
Plerixafor-associated Adverse Events
time frame: 100 Days Post Transplant

Secondary Outcomes

Measure
Transplant Related Mortality Calculated at Day +100
time frame: 100 Days Post Transplant
Immunological Reconstitution
time frame: 90 days
Plasma Cytokines/Chemokines
time frame: 1 month
Incidence of Grade II/IV Acute Graft Versus Host Disease
time frame: 100 days

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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.

Additional Information

Official title A Phase I/II Study: Enhancing Donor Hematopoietic Cell Engraftment With Plerixafor in Myeloablative Allogeneic Hematopoietic Cell Transplantation
Principal investigator Mitchell Horwitz, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Duke University.