Randomised Placebo-Controlled Double-Blind Phase II Study Applying Palifermin to Improve T-cell Immune Reconstitution After Haploidentical Allogeneic Peripheral Blood Progenitor Cell (PBPC) Transplantation
Inclusion Criteria:
Recipient:
- Chemosensitive low/high grade B-NHL or T-NHL, Multiple Myeloma (MM) in partial or
complete remission
- ALL and AML, secondary AML and biphenotypic acute leukemia in complete remission (CR1
or CR2) or PR (only if ≤20% blasts in BM), Myelodysplastic syndrome (MDS)
- CML in chronic or accelerated phase
- Osteomyelofibrosis (OMF)
- Hodgkin lymphoma (HD) in partial or complete remission
- Age ≥18 years, ≤ 65 years
- ECOG status ≤2
- Prior treatment with 3 or less different chemotherapy regimens (not cycles); prior
local radiotherapy is allowed except radiation involving the thymus
- Adequate pulmonary function
- Left ventricular ejection fraction (LVEF) >30%
- Haploidentical related donor
- Failure to find matched related or matched unrelated donor and urgently requiring
transplantation
- Planned conditioning regimen per Aversa or Würzburg protocol
- Women must be post-menopausal, sterile or use effective contraception and have a
negative pregnancy test at study entry (β-HCG neg)
- Signed informed consent
Donor:
- Healthy family member
- Selection based on typing of HLA-A, B, C, DR loci. Donor must be at least
genotypically HLA-A, B, C, DR haploidentical to the patient, but must differ for 2-3
HLA allele(s) on the unshared haplotype
- Donors must be capable of undergoing leukapheresis, have adequate venous access, and
be willing to undergo insertion of a central venous catheter should leukapheresis via
peripheral vein be inadequate.
- Donors must agree to a 2nd donation of PBPCs in case of insufficient CD34+ cell
collection or should patient fail to demonstrate sustained engraftment
- Signed informed consent
Exclusion Criteria:
Recipient:
- History of or concurrent cancer (< 5 years ago) other than those named in inclusion
criteria
- Primary chemorefractory disease
- CML in blast crisis
- MM with no or minor response to previous treatment
- Prior treatment with palifermin, or other keratinocyte growth factors
- Documented hypersensitivity to palifermin, E. coli-derived proteins, or any component
of the product
- Documented hypersensitivity to Prevenar vaccine or its components
- Prior allogeneic or tandem PBPC transplantation (no more than 1 previous autologous
transplantation
- Prior total body irradiation
- Post thymectomy
- Major anticipated illness or organ failure incompatible with survival from PBPC
transplantation
- Active chronic skin disease requiring therapy
- Active inflammatory bowel disease requiring therapy
- Active uncontrolled infection
- Sero-positive HIV
- Pregnancy or breast-feeding
- Active invasive fungal tissue infection (EORTC criteria)
- 30 days or less since receiving an investigational product or device in another
clinical trial
- Concurrent enrolment in another trial is not permitted unless the purpose is for
long-term follow-up/survival data only, or observational only
- Chronic pancreatitis or history of acute pancreatitis within 1 year prior to
transplant
- Psychiatric disorder associated with incompliance
- Myocardial infarction less than 3 months pre enrolment or EF <30% as measured in
echocardiography/laevoventriculography
- Infusion of retrovirally or other transduced cells are not permitted.
- Planned intravenous application of immunoglobulins is contraindicated throughout the
study period.
- Donor lymphocyte infusions are not allowed.
Donor:
- A positive HIV or HTLV-1 test or evidence of active/persistent viral hepatitis
infection.
- Evidence of any other active infection
- Any medical condition (i.e. insulin-dependent diabetes, cardiovascular disorders,
chronic inflammatory diseases) posing a health risk for peripheral blood stem cell
harvest
- Hematopoietic or marrow function related disease interfering with the collection of
sufficient numbers of normal progenitor cells
- Pregnancy or breast-feeding
- Any malignancy besides basal cell epithelioma or cured malignancy < 5 years ago
- Psychiatric disorder associated with incompliance