Main info

Identifier:

HO107 MOBILIZATION

Sponsor:

HOVON

Working group party:

SCT & Supportive care

Age:

18-60

Echelon:

Level A

Included patients:

38

(of 60)

Active sites:

4

(of 4)

Title:

The feasibility and efficacy of subcutaneous Plerixafor for mobilization of peripheral blood stem cells in allogeneic HLA–identical sibling donors: a prospective phase II study.

Timeline

News

Flow

Details

Phase:

Prospective Phase II study

Monitoring Type:

Not any more

Objectives:

Primary Objective:

• To determine the feasibility of plerixafor 320 μg/kg subcutaneously to harvest a sufficient number of peripheral blood stem cells in healthy HLA-matched sibling donors.

Feasibility will be defined as follows: A harvest of at least 2x10^6 CD34+ cells/kg recipient body weight cells in one or two aphereses in at least 90% of the donors A harvest of at least 2x10^6 CD34+ cells/kg cells in one or two aphereses in 70% or less of the donors
will be considered as failure.

Secondary Objectives:
Donors

• To determine the efficacy of plerixafor subcutaneous. Efficacy will be determined as follows: The absolute number of CD34+ cells collected in 1 liter processed volume.
• To determine the time interval that is required to obtain 2.0x 106 CD34 + cells from start of mobilization procedure
• Pharmacokinetics: to determine the number of CD34+ cells in the peripheral blood at regular intervals after the administration of plerixafor.
• To determine the number of CD34+ cells in the peripheral blood as well as in the collected stem cells at regular intervals during the stem cell apheresis.
• To determine the phenotype of plerixafor mobilized and collected CD34+ cells including progenitor cells, dendritic cells and regulatory T-cells both in peripheral blood and collected stem cells.
• To document adverse events grade 1-4 during and directly following mobilization by plerixafor 320 μg/kg subcutaneously.

Patients

• To document engraftment 30, 60 and 90 days after transplantation with an allograft harvested after mobilization with plerixafor 320 μg/kg subcutaneous. Engraftment is defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) of at least 0.5 ×10^9/l
• To document the day of hematopoietic reconstitution for neutrophils and platelets. This is defined as the first of 3 consecutive days of ANC ≥ 0.5x 10^6/L and platelets > 50x10^9/L
• 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.
• To evaluate the incidence and grade of graft versus host disease (GVHD).

Eligibility

Inclusion Criteria:

HLA identical sibling donor

• Age 18-60 years inclusive
• Hematologic parameters within normal limits
• Capable of undergoing leucapheresis: adequate venous access. Must be willing to undergo insertion of a central catheter should leucapheresis via peripheral vein be inadequate
• Willing and able to have bone marrow aspiration if there is mobilization failure
• Negative pregnancy test at study entry for women of childbearing potential
• Willing and able to use adequate contraception during the mobilization period and up to 3 months after last dose of plerixafor
• Written informed consent from donor

Patient inclusion criteria

• Age 18-65 years inclusive
• In general, indication for allogeneic stem cell transplant will be determined by each participating center according to local criteria.
• Patients with a cytopathologically confirmed diagnosis of:
  • De novo Acute Myeloid Leukemia according to WHO classification in first complete remission (excluding acute promyelocytic leukemia)
  • Therapy related AML/RAEB in first complete remission
  • Myelodysplasia RA(RS)/RCMD with IPSS ≥ 1.5
  • Myelodysplasia refractory anemia with excess of blasts (RAEB) with IPSS ≥ 1.5 in first complete remission
  • Biphenotypic leukemia in first complete remission OR
  • De novo B or T Lineage Acute Lymphatic Leukemia in first complete remission.
  • Multiple myeloma, not included in other transplant study
  • Hodgkin Lymphoma
  • Non-Hodgkin lymphoma
  • Chronic lymfocytic leukemia
  • Chronic myeloid leukemia
• WHO performance score 0,1 or 2
• Patients should have an HLA- identical sibling donor
• Life expectancy >3 months
• Negative pregnancy test at study entry for women of childbearing potential
• Willing and able to use adequate contraception
• Written informed consent from patient

Exclusion Criteria:

Donor exclusion criteria

• Monozygotic twin
• Unstable hypertension requiring more than 1 medication.
• Positive serology for hepatitis C or HbsAg
• Treatment with other investigational drugs
• HIV positivity
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• Pregnant or breastfeeding female subject

Patient exclusion criteria

• Cardiac dysfunction as defined by:
  • Myocardial infarction within the last 6 months of study entry
  • Reduced left ventricular function with an ejection fraction < 50% as measured by MUGA scan or echocardiogram,
  • Unstable angina
  • Unstable cardiac arrhythmias
• Severe pulmonary dysfunction (CTCAE grade 3-4, see appendix B)
• Severe neurological or psychiatric disease
• Significant hepatic dysfunction (serum bilirubin ≥ 1.5 times upper limit of normal or transaminases ≥ 2.5 times upper limit of normal)
• Significant renal dysfunction (creatinine clearance < 50 ml/min after rehydration)
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
• Patient known to be HIV-positive
• Pregnant or breast-feeding female patients.
• Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Presence of other active non-hematological malignancy

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals