KGF Haplo Allo: Palifermin After Haploidentical PBSCT

Sponsor

European Society for Blood and Marrow Transplantation (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00570999

Collaborator

Amgen (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a double blind, placebo controlled clinical trial, where patients with an advanced form of blood cancer are treated with haploidentical allogeneic peripheral blood progenitor cell (PBPC) transplant after which they are randomised to receive either placebo or a keratinocyte growth factor (Palifermin or Kepivance®).

The function of Kepivance® is to stimulate the growth of epithelial cells. This drug has also been suggested to have an ability to help improve the reconstitution, or development, of the immune system after the transplantation.

The hypothesis is that the patients T-cell dependent humoral immune response to recall antigen (PrevenarTM) will be higher in in palifermin treated patients than in the placebo control group

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma or Hodgkin's Disease Acute Leukaemia Myelodysplastic Syndrome Chronic Myeloid Leukemia Osteomyelofibrosis	Drug: Palifermin Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2008

Anticipated Study Completion Date :

Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Palifermin once daily at a dose of 60 mg/kg/day for 3 days before the start of the conditioning regimen and then for 3 consecutive days starting on the day of transplantation (days 0 to day +2 inclusively).	Drug: Palifermin 60 mg/kg/day Other Names: Keratinocyte growth factor Kepivacine
Placebo Comparator: Arm B Placebo at a dose of 1.2 mL (saline 0,9%) once daily for 3 days before the start of the conditioning regimen and then for 3 consecutive days starting on the day of transplantation (days 0 to day +2 inclusively).	Other: Placebo 1,2 mL once daily Other Names: 0.9% saline

Arm

Intervention/Treatment

Experimental: Arm A

Palifermin once daily at a dose of 60 mg/kg/day for 3 days before the start of the conditioning regimen and then for 3 consecutive days starting on the day of transplantation (days 0 to day +2 inclusively).

Drug: Palifermin

60 mg/kg/day

Other Names:

Keratinocyte growth factor

Kepivacine

Placebo Comparator: Arm B

Placebo at a dose of 1.2 mL (saline 0,9%) once daily for 3 days before the start of the conditioning regimen and then for 3 consecutive days starting on the day of transplantation (days 0 to day +2 inclusively).

Other: Placebo

1,2 mL once daily

Other Names:

0.9% saline

Outcome Measures

Primary Outcome Measures

To test palifermin's effect on the T-cell dependent humoral immune response to recall antigen (Prevenar™) [at study day +270 (20 days after the third Prevenar injection)]

Secondary Outcome Measures

To assess if Palifermin improves T-cell reconstitution after haploidentical allogeneic transplantation [at study days: +240]
To assess if Palifermin improves T-cell reconstitution after haploidentical allogeneic transplantation [Study days +210, +240, +270]
To assess disease free survival (DFS) and overall survival (OS), incidence and duration of GvHD, incidence and severity of OM, and incidence and severity of infections [at 2 years]
To assess drug related safety [at 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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