Primary objectiveTo determine the feasibility of plerixafor 320 *g/kg subcutaneously to harvest a sufficient number of CD34+ peripheral blood stem cells/kg recipient body weight. Feasibilty is defined as a minimum of 2.0x10^6/kg CD34+ cells in one…
ID
Source
Brief title
Condition
- Other condition
- Leukaemias
Synonym
Health condition
stamcel mobilisatie bij donoren
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage of donors with a successful harvest (*2.0x106 CD34+ cells /kg).
Secondary outcome
For donors:
1. The absolute number of CD34+ cells collected per litre processed volume.
2. The time required to collect 2.0x10^6CD34+ cells/kg, also in relation to the
time of administration of plerixafor.
3. The number of CD34+ cells in the peripheral blood at regular intervals after
the administration of plerixafor.
4. 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. The phenotype of CD34+ cells and hematopoietic progenitor cells including
its subpopulations, dendritic cells as well as regulatory T-cells in the graft.
6. The incidence and CTCAE grade (1-4) of adverse events.
For patients:
1. incidence of engraftment at days 30, 60 and 90 after transplantation with
plerixafor mobilized HPCs.
2. time to hematopoietic reconstitution.
3. hematopoietic chimerism in blood, CD3 isolated cells at days 30, 60, 90
after transplantation and in bone marrow at day 90 after transplantation.
4. incidence and grade of GVHD..
Background summary
The 4-5 days administration of G-CSFsubcutaneously twice daily for mobilization
of allogeneic hematopoietic progenitor cells (HPCs) nowadays is standard but
accompanied by several grade 2 and 3 side effects in about 70% of the
allogeneic donors. Preliminary studies showed that a single subcutaneous
injection of plerixafor a CXCR4/SDF1 antagonist results in direct release of
HPCs with limited toxicities. Patients engrafted with allogeneic HPCs that were
collected after plerixafor mobilization showed rapid and complete engraftment.
Also plerixafor seems to mobilize a more primitive stem cell subset that might
result in better engraftment in comparison to G-CSF. The peak level of CD34+
cells after plerixafor subcutaneously is seen after 8-9 hours. The proposed
prospective phase II study intends to evaluate subcutaneous plerixafor 320 *g/
kg to mobilize HPCs from healthy HLA-matched adult sibling donors.
Study objective
Primary objective
To determine the feasibility of plerixafor 320 *g/kg subcutaneously to harvest
a sufficient number of CD34+ peripheral blood stem cells/kg recipient body
weight.
Feasibilty is defined as a minimum of 2.0x10^6/kg CD34+ cells in one or two
phereses in at least 90% of the donors
Study design
The study will be performed as a prospective phase II study
Intervention
Donors will receive plerixafor 320 *g/kg subcutaneously
Patients will be transplanted with the stem cells harvested with plerixafor
according to standard practice
Study burden and risks
Instead of 4-5 days administration of G-CSF subcutaneously twice daily, donors
will receive a single injection of plerixafor subcutaneously 9 hours before the
planned stem cell collection. In case less than 2.0 x 10^6 CD34+ cells/kg are
collected the procedure can be repeated the following day. Before and during
the stem cell collection extra blood samples will be drawn. After the procedure
donors will have to make 3 visits to the hospital the first year and 1 in the
second year.
Plerixafor seems safe in a large number of patients and a limited number of
healthy volunteers. Side effects are in general no more than grade 2 and
consist mainly of lightheadeiness, nausea, flatulence, injection site
discomfort.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Donors
* 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 ;Patients
* 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
Donors
* Monozygotic twin
* Unstable hypertension requiring more than 1 medication.
* Positive serology for hepatitis C or HbsAg
* Treatment with other investigational drugs
* HIV positivity
* Pregnant or breastfeeding female subject;Patients
* Cardiac dysfunction
* Severe pulmonary dysfunction (CTCAE grade 3-4)
* Severe neurological or psychiatric disease
* Significant hepatic dysfunction
* Significant renal dysfunction
* 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.
* Presence of other active non-hematological malignancy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-023436-16-NL |
| CCMO | NL34799.000.11 |