Allogeneic Hematopoietic Stem Cell Transplantation in Pancreatic Adenocarcinoma

July 4, 2023 updated by: Brigitta Omazic, Karolinska Institutet

Non Myeloablative Allogeneic Stem Cell Transplantation as Adjuvant Treatment in Patients With Pancreatic Adenocarcinoma

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?

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Sweden
      • Stockholm, Sweden, 141 86
        • Center for allogeneic stem cell transplantation, Karolinska University hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with pancreatic adenocarcinoma who have undergone curative surgery ad modum Whipple with radical resection of the tumor, R0 or R1.

Exclusion Criteria:

  • Pancreatic adenocarcinoma with metastasis or non-radical resection.
  • Recurrence of the malignancy after curative surgery and adjuvant chemotherapy.
  • Age above 70 years.
  • Severe heart disease, liver disease, impaired renal function or other organ failure or underlying diseases that would exclude the patient from undergoing hematopoietic stem cell transplantation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Hematopoetic stem cell transplantation
Patients with pancreatic adenocarcinoma that have undergone Whipple surgery and show no sign of disease recurrence can be treated with hematopoietic stem cell transplantation to achieve an immunological anti-tumor effect.
Procedure: Allogeneic hematopoietic stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
disease free survival
Time Frame: Five years
Five years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Karolinska Institutet

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Karolinska University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 18, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2014

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 4, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PANCHSCT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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