Hematologic MalignanciesPhase 2CIK2NCT01186809
Cytokine Induced Killer (CIK) Cells In Leukemia Patients
A Phase 2 study testing in vitro expanded Cytokine Induced Killer (CIK) cells in people with Hematologic Malignancies, run by A.O. Ospedale Papa Giovanni XXIII at 3 sites in Italy.
Trial summary
The purpose of the Phase IIA study are to: 1. define the safety profile 2. evaluate the efficacy of a sequential infusion of unmanipulated Donor Lymphocyte Infusions (DLI) and Cytokine Induced Killer (CIK) cells for the treatment of molecular, cytogenetic or hematologic relapse after hematopoietic stem cell… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- in vitro expanded Cytokine Induced Killer (CIK) cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 3 sitesItaly
- Study dates
- Jul 2009to 15 May 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with haematologic malignancies (excluding chronic myeloid Leukemia- CML) with a molecular, cytogenetic or haematologic relapse after allogeneic transplantation.
- Patients with an available donor willing to donate peripheral blood lymphocytes
- Immunosuppression must be withdrawn at the beginning of the cell therapy program
- Written informed consent prior to any study procedures being performed
Who cannot join
- Donors positive for HIV, HBV or HCV, or unfit to undergo leukapheresis
- Patients with active acute or chronic Graft versus host disease (GvHD)
- Patients with rapidly progressive disease or not controlled by palliative supportive treatments including chemotherapy and with a life expectancy less than 8 weeks
- Patients with severe psychiatric illness or any disorder that compromises ability to give truly informed consent for participation in this study
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
Azienda Ospedaliera Papa Giovanni XXIII (Former:Ospedali Riuniti di Bergamo) Bergamo
Bergamo, 24127
Ospedale Centrale di Bolzano
Bolzano
Ospedale San Gerardo
Monza
About this study
Official title: Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK)Cells After Allogeneic Stem Cell Transplantation
The purpose of the Phase IIA study are to:
- define the safety profile
- evaluate the efficacy of a sequential infusion of unmanipulated Donor Lymphocyte Infusions (DLI) and Cytokine Induced Killer (CIK) cells for the treatment of molecular, cytogenetic or hematologic relapse after hematopoietic stem cell transplantation and The progression free survival and the overall survival after the sequential infusion of Donor Lymphocyte Infusions (DLI) and Cytokine Induced Killer(CIK) cells.
Read the detailed description
This study is an open-label, multicenter, exploratory phase IIA study to evaluate the safety (dose-finding) and efficacy of a sequential administration of donor derived unmanipulated DLI and in vitro expanded Cytokine Induced Killer(CIK) cells.
Two infusions of unmanipulated donor lymphocytes (1x106/Kg each) will be given with a minimum interval of 3 weeks. Three infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). In presence of grade 2 or more acute graft versus host disease(GVHD), the patient will not receive the next scheduled infusion. Only grade 4 acute graft versus host disease (aGVHD) is considered for the dose limiting toxicity (DLT). Once identified the maximally tolerated dose (MTD), this same combination of doses will be administered up to 24 patients in a two-stage minimax design.
Primary Endpoints
The primary endpoints of the Phase IIA study are:
- the Maximally Tolerated Dose (MTD) - (safety end-point)
- the cumulative incidence of molecular, karyotypic or haematologic responses at day +100 after the end of the cell therapy program - (efficacy end-point)
Secondary Endpoints Progression Free Survival (PFS) Progression Free Survival (PFS) will be defined as any evidence of molecular, cytogenetic or haematologic disease progression. Cytogenetic and/or molecular relapse will be defined where available as any evidence of a pre-transplant defined abnormality using conventional cytogenetics or FISH techniques or molecular probes. Assessments will be performed at 1 year after the end of the cell therapy program Overall Survival (OS) The Overall Survival(OS) will be assessed by 1 year after the end of the cell therapy program. For assessment of the Overall Survival (OS), events will be deaths for any causes, patients being censored if alive.
- Conditions
- Hematologic Malignancies
- Being tested
- in vitro expanded Cytokine Induced Killer (CIK) cells
- Keywords
- hematologic malignancies (excluding Chronic Myeloid Leukemia)
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
in vitro expanded Cytokine Induced Killer (CIK) cellsBiological
Also called patients will be offered Cytokine Induced Killer(CIK) cells., Four combinations of escalating Cytokine Induced Killer (CIK) cells infusions will be provided, until the MTD will be defined., Combination 1st CIK cells infusion 2nd CIK cells infusion 3rd CIK cells infusion, 1 1x106/Kg 1x106/Kg 5x106/kg
Three infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). Cytokine Induced Killer administrations will be separated by 3 weeks intervals
| Study group | Role | What they receive |
|---|---|---|
| Cytokine Induced Killer | Experimental | Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK) Receives: Biological: in vitro expanded Cytokine Induced Killer (CIK) cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Measures
The occurrence of a grade 4 acute graft versus host disease (GVHD), judged to be related to the study medication. Grading and staging will be performed using the Glucksberg scale
Measured: Clinical response was measured at 100 days after the completion of the cell therapy program.
Secondary outcomes (1)
Efficacy Measures
The proportion of patients achieving a complete, a partial or a hematologic improvement in responses to the experimental infusion of cytokine induced killer (CIK)cells
Measured: The clinical response will be registered at day +100 after the last Cytokine Induced Killer (CIK) cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2010 (estimated)
- Study startJul 2009
- Primary completionSep 2016
- Study completion15 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- A.O. Ospedale Papa Giovanni XXIII
- Sponsor type
- University, hospital or other
- Collaborators
- Regional Hospital of Bolzano, Azienda Ospedaliera San Gerardo di Monza
- Responsible party
- Principal investigator, Rambaldi Alessandro, A.O. Ospedale Papa Giovanni XXIII
- Investigators
- Alessandro AR Rambaldi, Professor, Principal investigator, Azienda Ospedaliera Papa Giovanni XXIII (Former:Ospedali Riuniti di Bergamo)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01186809
- Sponsor's protocol ID
- Eudract number: 2008-003185-26
- Acronym
- CIK2
- Status last verified
- Jan 2019
- First submitted
- 10 Aug 2010
- Last updated
- 23 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: final report
Publications
Introna M, Franceschetti M, Ciocca A, Borleri G, Conti E, Golay J, Rambaldi A. Rapid and massive expansion of cord blood-derived cytokine-induced killer cells: an innovative proposal for the treatment of leukemia relapse after cord blood transplantation. Bone Marrow Transplant. 2006 Nov;38(9):621-7. doi: 10.1038/sj.bmt.1705503. Epub 2006 Sep 18.
PubMed 16980990Introna M, Borleri G, Conti E, Franceschetti M, Barbui AM, Broady R, Dander E, Gaipa G, D'Amico G, Biagi E, Parma M, Pogliani EM, Spinelli O, Baronciani D, Grassi A, Golay J, Barbui T, Biondi A, Rambaldi A. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study. Haematologica. 2007 Jul;92(7):952-9. doi: 10.3324/haematol.11132.
PubMed 17606446Capelli C, Salvade A, Pedrini O, Barbui V, Gotti E, Borleri G, Cabiati B, Belotti D, Perseghin P, Bellavita P, Biondi A, Biagi E, Rambaldi A, Golay J, Introna M. The washouts of discarded bone marrow collection bags and filters are a very abundant source of hMSCs. Cytotherapy. 2009;11(4):403-13. doi: 10.1080/14653240902960437.
PubMed 19462317Introna M, Pievani A, Borleri G, Capelli C, Algarotti A, Mico C, Grassi A, Oldani E, Golay J, Rambaldi A. Feasibility and safety of adoptive immunotherapy with CIK cells after cord blood transplantation. Biol Blood Marrow Transplant. 2010 Nov;16(11):1603-7. doi: 10.1016/j.bbmt.2010.05.015. Epub 2010 Jun 1.
PubMed 20685246
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK)Cells After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01186809
- Acronym / sponsor ID
- CIK2 / Eudract number: 2008-003185-26
- Conditions
- Hematologic Malignancies
- Keywords
- hematologic malignancies (excluding Chronic Myeloid Leukemia)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- A.O. Ospedale Papa Giovanni XXIIIUniversity, hospital or other
- Collaborators
- Regional Hospital of Bolzano, Azienda Ospedaliera San Gerardo di Monza
- Study start
- Jul 2009
- Primary completion
- Sep 2016 (actual)
- Study completion
- 15 May 2017 (actual)
- First posted
- 23 Aug 2010 (estimated)
- Results
- Posted 23 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the Phase IIA study are to:
- define the safety profile
- evaluate the efficacy of a sequential infusion of unmanipulated Donor Lymphocyte Infusions (DLI) and Cytokine Induced Killer (CIK) cells for the treatment of molecular, cytogenetic or hematologic relapse after hematopoietic stem cell transplantation and The progression free survival and the overall survival after the sequential infusion of Donor Lymphocyte Infusions (DLI) and Cytokine Induced Killer(CIK) cells.
Detailed description
This study is an open-label, multicenter, exploratory phase IIA study to evaluate the safety (dose-finding) and efficacy of a sequential administration of donor derived unmanipulated DLI and in vitro expanded Cytokine Induced Killer(CIK) cells.
Two infusions of unmanipulated donor lymphocytes (1x106/Kg each) will be given with a minimum interval of 3 weeks. Three infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). In presence of grade 2 or more acute graft versus host disease(GVHD), the patient will not receive the next scheduled infusion. Only grade 4 acute graft versus host disease (aGVHD) is considered for the dose limiting toxicity (DLT). Once identified the maximally tolerated dose (MTD), this same combination of doses will be administered up to 24 patients in a two-stage minimax design.
Primary Endpoints
The primary endpoints of the Phase IIA study are:
- the Maximally Tolerated Dose (MTD) - (safety end-point)
- the cumulative incidence of molecular, karyotypic or haematologic responses at day +100 after the end of the cell therapy program - (efficacy end-point)
Secondary Endpoints Progression Free Survival (PFS) Progression Free Survival (PFS) will be defined as any evidence of molecular, cytogenetic or haematologic disease progression. Cytogenetic and/or molecular relapse will be defined where available as any evidence of a pre-transplant defined abnormality using conventional cytogenetics or FISH techniques or molecular probes. Assessments will be performed at 1 year after the end of the cell therapy program Overall Survival (OS) The Overall Survival(OS) will be assessed by 1 year after the end of the cell therapy program. For assessment of the Overall Survival (OS), events will be deaths for any causes, patients being censored if alive.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cytokine Induced Killer | Experimental | Biological: in vitro expanded Cytokine Induced Killer (CIK) cellsSequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with haematologic malignancies (excluding chronic myeloid Leukemia- CML) with a molecular, cytogenetic or haematologic relapse after allogeneic transplantation.
- Patients with an available donor willing to donate peripheral blood lymphocytes
- Immunosuppression must be withdrawn at the beginning of the cell therapy program
- Written informed consent prior to any study procedures being performed
Key exclusion criteria (4 listed)
- Donors positive for HIV, HBV or HCV, or unfit to undergo leukapheresis
- Patients with active acute or chronic Graft versus host disease (GvHD)
- Patients with rapidly progressive disease or not controlled by palliative supportive treatments including chemotherapy and with a life expectancy less than 8 weeks
- Patients with severe psychiatric illness or any disorder that compromises ability to give truly informed consent for participation in this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| in vitro expanded Cytokine Induced Killer (CIK) cellsAlso: patients will be offered Cytokine Induced Killer(CIK) cells., Four combinations of escalating Cytokine Induced Killer (CIK) cells infusions will be provided, until the MTD will be defined., Combination 1st CIK cells infusion 2nd CIK cells infusion 3rd CIK cells infusion, 1 1x106/Kg 1x106/Kg 5x106/kgThree infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). Cytokine Induced Killer administrations will be separated by 3 weeks intervals | Biological | Cytokine Induced Killer |
Primary outcome
Safety Measures
Time frame: Clinical response was measured at 100 days after the completion of the cell therapy program.
The occurrence of a grade 4 acute graft versus host disease (GVHD), judged to be related to the study medication. Grading and staging will be performed using the Glucksberg scale
1 secondary outcome
Efficacy Measures
Time frame: The clinical response will be registered at day +100 after the last Cytokine Induced Killer (CIK) cell infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 16980990Introna M, Franceschetti M, Ciocca A, Borleri G, Conti E, Golay J, Rambaldi A. Rapid and massive expansion of cord blood-derived cytokine-induced killer cells: an innovative proposal for the treatment of leukemia relapse after cord blood transplantation. Bone Marrow Transplant. 2006 Nov;38(9):621-7. doi: 10.1038/sj.bmt.1705503. Epub 2006 Sep 18.
- Results publication: PubMed 17606446Introna M, Borleri G, Conti E, Franceschetti M, Barbui AM, Broady R, Dander E, Gaipa G, D'Amico G, Biagi E, Parma M, Pogliani EM, Spinelli O, Baronciani D, Grassi A, Golay J, Barbui T, Biondi A, Rambaldi A. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study. Haematologica. 2007 Jul;92(7):952-9. doi: 10.3324/haematol.11132.
- Results publication: PubMed 19462317Capelli C, Salvade A, Pedrini O, Barbui V, Gotti E, Borleri G, Cabiati B, Belotti D, Perseghin P, Bellavita P, Biondi A, Biagi E, Rambaldi A, Golay J, Introna M. The washouts of discarded bone marrow collection bags and filters are a very abundant source of hMSCs. Cytotherapy. 2009;11(4):403-13. doi: 10.1080/14653240902960437.
- Results publication: PubMed 20685246Introna M, Pievani A, Borleri G, Capelli C, Algarotti A, Mico C, Grassi A, Oldani E, Golay J, Rambaldi A. Feasibility and safety of adoptive immunotherapy with CIK cells after cord blood transplantation. Biol Blood Marrow Transplant. 2010 Nov;16(11):1603-7. doi: 10.1016/j.bbmt.2010.05.015. Epub 2010 Jun 1.
- Individual participant dataSharing planned: Yes. final report
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessandro AR Rambaldi, Professor principal investigator
Azienda Ospedaliera Papa Giovanni XXIII (Former:Ospedali Riuniti di Bergamo)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing in vitro expanded Cytokine Induced Killer (CIK) cells in people with Hematologic Malignancies, run by A.O. Ospedale Papa Giovanni XXIII at 3 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Measures (time frame: Clinical response was measured at 100 days after the completion of the cell therapy program.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01186809, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2019.