Clinical trial NCT01280955: Donor Enhancement With Plerixafor Post Myeloablative Allogeneic Transplant
Official title: A Phase I/II Study: Enhancing Donor Hematopoietic Cell Engraftment With Plerixafor in Myeloablative Allogeneic Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Failure of Bone Marrow Graft
Keywords: Plerixafor and Allogeneic Myeloablative Stem Cell Transplant
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2011-01-21
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Time to Neutrophil Recovery
timeFrame: 100 Days post Transplant
measure: Time to Platelet Recovery
timeFrame: 100 Days Post Transplant
measure: Plerixafor-associated Adverse Events
timeFrame: 100 Days Post Transplant
Secondary outcomes:
measure: Transplant-related Mortality
timeFrame: 100 Days Post Transplant
measure: Absolute Lymphocyte Count at Day 90
timeFrame: 90 days
measure: IL-12 at Day 30
timeFrame: 30 days
measure: Participants Experiencing Grade II-IV Acute Graft Versus Host Disease
timeFrame: 100 days
measure: CD3+ Cell Count at Day 90
timeFrame: 90 Days
measure: CD4 Cell Count at Day 90
timeFrame: 90 days
measure: CD8 Cell Count at Day 90
timeFrame: 90 days
measure: NK Cell Count at Day 90
timeFrame: 90 days
measure: B Cell Count at Day 90
timeFrame: 90 days
measure: IFN Gamma at Day 30
timeFrame: 30 days
measure: TNF-alpha at Day 30
timeFrame: 30 days
measure: CD4 Cell Count at Day 30
timeFrame: 30 days
measure: CD4 Cell Count at Day 60
timeFrame: 60 days
measure: CD8 Cell Count at Day 30
timeFrame: 30 days
measure: CD8 Cell Count at Day 60
timeFrame: 60 days
measure: NK Cell Count at Day 30
timeFrame: 30 days
measure: NK Cell Count at Day 60
timeFrame: 60 days
measure: B Cell Count at Day 30
timeFrame: 30 days
measure: B Cell Count at Day 60
timeFrame: 60 days
measure: IL-12 at Day 7
timeFrame: 7 days
measure: IL-12 at Day 14
timeFrame: 14 days
measure: IFN Gamma at Day 7
timeFrame: 7 days
measure: IFN Gamma at Day 14
timeFrame: 14 days
measure: TNF-alpha at Day 7
timeFrame: 7 days
measure: TNF-alpha at Day 14
timeFrame: 14 days
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Duke University
name: Mitchell Horwitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Saurabh Chhabra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.