Stem cell mobilization in healthy HLA- matched adult sibling donors with plerixafor. Patients diagnosed with Leukemia/myelodysplasia eligible for allogeneic stem cell transplantation
Conditions
Interventions
Arm A: Donors will receive plerixafor 320 μ
g/kg subcutaneously
Arm B: Donors will receive plerixafor 320 μ
g/kg intravenously.
Sponsors
Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)
P/a HOVON Data Center
Erasmus MC - Daniel den Hoed
P.O. box 5201
3008 AE Rotterdam
Tel: +31 10 7041560
Fax: +31 10 7041028
e-mail: hdc@erasmusmc.nl
Eligibility
Inclusion criteria
Inclusion criteria: Donors: 1. HLA identical sibling donor; 2. Age 18-60 years inclusive; 3. Hematologic parameters within normal limits; 4. Capable of undergoing leucapheresis: Adequate venous access. Must be willing to undergo insertion of a central catheter should leucapheresis via peripheral vein be inadequate; 5. Willing and able to have bone marrow aspiration if there is mobilization failure; 6. Negative pregnancy test at study entry for women of childbearing potential; 7. Willing and able to use adequate contraception during the mobilization and collection period; 8. Written informed consent from donor. Patients: 1. Age 18-65 years inclusive; 2. Patients with a cytopathologically confirmed diagnosis of: A. De novo Acute Myeloid Leukemia according to WHO classification in first complete remission (excluding acute promyelocytic leukemia) OR; B. Myelodysplasia refractory anemia with excess of blasts (RAEB) with IPSS ≥ 1.5 in first complete remission OR; C. Therapy related AML/RAEB in first complete remission OR; D. Biphenotypic leukemia in first complete remission OR; E. De novo B or T Lineage Acute Lymphatic Leukemia in first complete remission. 3. WHO performance score 0,1 or 2; 4. Patients should have an HLA-identical sibling donor; 5. Life expectancy >3 months; 6. Negative pregnancy test at study entry for women of childbearing potential; 7. Willing and able to use adequate contraception; 8. Written informed consent from patient.
Exclusion criteria
Exclusion criteria: Donors: 1. Monozygotic twin; 2. Unstable hypertension requiring more than 1 medication; 3. Positive serology for hepatitis C or HbsAg; 4. Treatment with other investigational drugs; 5. HIV positivity; 6. Pregnant or breastfeeding female subject. Patients: 1. Patients who are treated with a kinase-inhibitor; 2. Cardiac dysfunction; 3. Severe pulmonary dysfunction (CTCAE grade 3-4); 4. Severe neurological or psychiatric disease; 5. Significant hepatic dysfunction; 6. Significant renal dysfunction; 7. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.); 8. Patient known to be HIV-positive; 9. Pregnant or breast-feeding female patients; 10. Presence of other active malignancy or a history of active malignancy during the past 5 years, other than non melanoma skin cancer, stage 0 cervical carcinoma, or treated early-stage prostate cancer provided that prostate-specific antigen is within normal limits.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the feasibility of plerixafor 320 μg/kg subcutaneously and of plerixafor 320 μg/kg intravenously to harvest a sufficient number of CD34+ peripheral blood stem cells/kg recipient body weight. Feasibilty is defined as a minimum of 2.0x106/kg CD34+ cells in one or two phereses in at least 90% of the donors. | — |
Secondary
| Measure | Time frame |
|---|---|
| Donors: 1. To determine the efficacy of plerixafor in both arms Efficacy will be determined as follows: the absolute number of CD34+ cells collected per liter processed blood volume; 2. To determine the time interval that is required to obtain 2.0 x 106 CD34+ cells/kg from start of mobilization procedure; 3. Pharmacokinetics: To determine the number of CD34+ cells in the peripheral blood at regular intervals after the administration of plerixafor; 4. To determine the number of CD34+ cells in the peripheral blood as well as in the apheresis product at regular intervals during the stem cell apheresis; 5. To determine the phenotype of plerixafor mobilized CD34+ cells including progenitor cells, dendritic cells and regulatory T-cells both in peripheral blood and collected stem cells; 6. To document adverse events grade 2-4 following mobilization by plerixafor. Patients: 1. To document engraftment 30, 60 and 90 days after transplantation with an allograft harvested after mobilization with plerixafor 320 μg/kg subcutaneously or intravenously; 2. To document hematopietic reconstitution i.e neutrophils and patelets; 3. To study chimerism in peripheral blood and T-cells 30, 60 and 90 days, and chimerism in bone marrow 90 days after transplantation with an allograft harvested after mobilization with plerixafor 320 μg/kg subcutaneously or intravenously; 4. To evaluate the incidence and grade of graft versus host disease (GVHD). | — |
Contacts
Public ContactG.E. Greef, de
Dept. Hematologie Erasmus MC - Daniel den Hoed P.O. box 5201
Outcome results
None listed