Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02207985 |
| Other study ID # |
PANCHSCT |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
January 2007 |
| Est. completion date |
June 1, 2017 |
Study information
| Verified date |
July 2023 |
| Source |
Karolinska Institutet |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Aim:
To study the antitumour effect of reduced intensity conditioning (RIC) with allogeneic stem
cell transplantation (HSCT) in patients with pancreatic adenocarcinoma after radical
resection of the tumour and adjuvant treatment with standard chemotherapy.
Importance:
If investigators can accomplish an anti-tumour effect using RIC with HSCT as adjuvant
treatment in patients with pancreatic adenocarcinoma, it might increase the survival or even
cure patients in this group with very poor prognosis.
Primary scientific question:
Can investigators demonstrate an anti-tumour effect against pancreatic adenocarcinoma using
adjuvant treatment with HSCT?
Can investigators demonstrate an anti-tumour effect against pancreatic adenocarcinoma using
adjuvant treatment with HSCT?
Description:
Background Cancer of the pancreas is one of the most common cancer forms in Sweden.
Nine-hundred persons receive this diagnosis every year. The 5-year survival is very low,
between 5 and 15%, even in the cases where radical resection of the tumor can be performed.
This is probably due to minimal residual disease that cannot be diagnosed at the time of
surgery. It has recently been shown that micrometastases of pancreatic adenocarcinoma can be
detected in tissue samples from lymph nodes and bone marrow, using new sensitive
immunohistological methods. When radical resection of the tumour is performed, no
microscopically visible tumour is left, but even in this situation, local recurrence of the
disease is the most common cause of death in these patients. None of the so far studied
adjuvant treatments, irradiation or chemotherapy, has substantially improved the survival in
patients with pancreatic adenocarcinoma.
Allogeneic hematopoietic stem cell transplantation (HSCT) is an established curative
treatment for malignant blood diseases, mainly leukemia. Using the conventional form of HSCT,
where the patient undergoes a myeloablative conditioning with chemotherapy and irradiation,
will diminish the amount of malignant cells, but also create space in the bone marrow for the
donated stem cells. The myeloablative conditioning induces severe toxic effects, but the
patient is rescued by the transplantation of the donated hematopoietic stem cells. The new
stem cells will mature into an immune system that will react with the patient's cells, an
effect called graft-versus-host reaction (GVHD). It has been shown that the graft-versus-host
reaction correlates well with the curative anti-tumor effect. A mild GVH reaction will
diminish the risk of relapse, while a severe GVH reaction might be mortal. This anti-tumour
effect is mediated by white blood cells of the T-cell type. From this knowledge, the HSCT
technique has been developed and nowadays it is possible to use reduced intensity
conditioning (RIC). With reduced intensity conditioning using milder forms of chemotherapy,
the toxic effects can be reduced, but the immunosuppressive effect is enough to make sure
that the hematopoietic stem cells will engraft. Using RIC has lead to treatment of older
patients and the anti-tumor effect is just as efficient as with the myeloablative
conditioning.
Recently, RIC with HSCT has been used as adjuvant treatment against solid tumours, mainly
kidney cancer, colon cancer and breast cancer. An important part of the treatment consists of
additional infusion of donor lymphocyte infusions (DLI) after the transplantation to maintain
or increase the anti-tumour effect. At our clinic, we have treated about 50 patients with
solid tumours using RIC with HSCT. Most of our patients had kidney or colon cancer (19 and 16
patients, respectively), but also two patients with prostate cancer have been treated. About
ten patients with primary liver cancers have been treated with liver transplantation combined
with RIC with HSCT. The transplantation-related mortality in these patients is about 10-15%.
Aim:
To study the antitumour effect of RIC with HSCT in patients with pancreatic adenocarcinoma
after radical resection of the tumour and adjuvant treatment with standard chemotherapy.
Importance:
If investigators can accomplish an anti-tumour effect using RIC with HSCT as adjuvant
treatment in patients with pancreatic adenocarcinoma, it might increase the survival or even
cure patients in this group with very poor prognosis.
Primary scientific question:
Can investigators demonstrate an anti-tumour effect against pancreatic adenocarcinoma using
adjuvant treatment with HSCT?
Secondary scientific questions:
What side-effects will the patient suffer? Can survival be improved compared to standard
treatment of pancreatic adenocarcinoma? Is it possible to improve the results by using
cytotoxic T-cells against specific pancreatic adenocarcinoma antigens? Are there methods to
identify the patients that will have the best results from the treatment? How will quality of
life be affected?
Study plan:
The aim of the study is to evaluate the anti-tumour effect of treatment with RIC with HSCT in
patients with pancreatic adenocarcinoma. All patients will undergo curative surgery with
radical resection of the tumour and adjuvant standard chemotherapy with gemcitabine. HSCT
will be offered to patients with an HLA-identical sibling, a kind of biological
randomisation. The control group will consist of patients without an HLA-identical sibling,
or those declining HSCT.
Inclusion criteria:
Patients with radically resected pancreatic adenocarcinoma that have received adjuvant
treatment with standard chemotherapy after surgery.
Exclusion criteria:
Pancreatic adenocarcinoma with metastases or non-radical resection of the tumour. Relapse
during standard chemotherapy. Age above 70 years. Severe heart conditions, liver disease,
impaired kidney function or other organ dysfunction that will result in severe toxic effects
of the HSCT treatment.
Group A will undergo radical resection of the tumour and standard chemotherapy. About eight
months after surgery, they will undergo conditioning with cyclophosphamide and fludarabine
before transplantation of donated hematopoietic stem cells from their HLA-identical sibling
donors. The immunosuppressive treatment, which is given to diminish GVHD, will be tapered
quickly to make sure that the anti-tumour effect is as efficient and as fast as possible.
Further infusion of DLI will be given to increase or maintain anti-tumour effect in the cases
where the graft-versus-host reaction is missing or is very mild. The first DLI will be given
intravenously and the second one will be given in A. hepatica to induce a better local
effect, since metastases to the liver is a very common event. Conditioning and HSCT will be
performed at Centre for Allogeneic Hematopoietic Stem Cell Transplantation and that is also
where the follow-up of the patients will be performed. The surgical follow-up will be at the
surgical department. Group B will be treated with standard chemotherapy according to current
protocols at the department of oncology.
The clinical and laboratory parameters that will be registered are:
- Mortality
- Morbidity
- Time to relapse, will be controled with CT scans
- Quality of life
- Tumour markers
- Detection of cytotoxic T-lymphocytes that have the ability to react with pancreactic
adenocarcinoma from the patient as well as cell lines in vitro
- Detection of micrometastases in bone marrow.
