Hematologic MalignanciesPhase 1NCT00675831
Infusion of Donor Lymphocytes Depleted of CD25+ Regulatory T-cells in Patients With Relapsed Hematologic Malignancies
A Phase 1 study testing CliniMACS CD25 Reagent Device in people with Hematologic Malignancies, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
The purpose of this research study is to evaluate the safety and efficacy of cell depletion in a donor lymphocyte infusion (DLI) product with the use of the CliniMACS machine. Previously, patients with hematologic malignancies who have relapsed after transplant have been given infusions of donor white blood cells… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- CliniMACS CD25 Reagent Device
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with hematologic malignancies that have relapsed after HLA-A, -B, -C, and-DRBI matched allogeneic hematopoietic stem cell transplantation
- At least 2 months following hematopoietic stem cell transplantation
- Off any systemic immunosuppressive medication for treatment or prevention of GVHD, for a minimum of 2 weeks prior to study entry
- Recipient with donor chimerism of 20% or greater within 6 weeks prior to DLI
- Patient with less than 50% bone marrow involvement (% cellularity) and less than 5cm lymph nodes, in the 6 weeks prior to DLI
- 18 years of age or older
- ECOG Performance Status score 0-2
- Prior stem cell donor is medically fit to undergo leukapheresis procedure
Who cannot join
- Relapsed CML in chronic phase
- Prior donor lymphocyte infusion or other immunotherapy treatment within 8 weeks prior to enrollment
- Chemotherapy within 4 weeks prior to enrollment
- Clinically significant and active autoimmune disease in donor or patient. This is defined as autoimmune disease resulting in organ dysfunction and/or requiring systemic therapy
- Evidence of active acute or chronic GVHD
- Uncontrolled infection
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: Infusion of Donor Lymphocytes Depleted of CD25+ Regulatory T-cells in Patients With Relapsed Hematologic Malignancies After Matched Allogeneic Hematopoietic Stem Cell Transplantation
The purpose of this research study is to evaluate the safety and efficacy of cell depletion in a donor lymphocyte infusion (DLI) product with the use of the CliniMACS machine. Previously, patients with hematologic malignancies who have relapsed after transplant have been given infusions of donor white blood cells calsed donor lymphocyte infusion (DLI) as a way to boost their immune function and fight cancer. Information from other research studies suggests that lowering the number of a certain type of white blood cell called CD25+ Tregs in the DLI may allow for a greater effect. In this research study, we are looking for the appropriate dose of DLI depleted of the CD25+ Treg white blood cells that can be given safely.
Read the detailed description
- The original marrow/stem cell donor will undergo one or two white blood cell collection procedures called leukopheresis. The cells collected from the first leukopheresis will be sent to the laboratory where the amount of white blood cells collected will be measured. If the number of cells collected at the first leukopheresis is not enough, the donor will have a second leukopheresis procedure.
- Once enough lymphocytes are collected from the donor, the CliniMACS CD25 Reagent System device will reduce the number of CD25+ Tregs. The CD25+ depleted donor lymphocytes will then be infused to the participant intravenously. Participants will be observed for about one hour after the infusion.
- One, two, four and eight weeks after the DLI, participants will return to the clinic for follow-up visits. At each visit a physical exam, questions about the participants general health, and blood tests will be performed.
- Conditions
- Hematologic Malignancies
- Being tested
- CliniMACS CD25 Reagent Device
- Keywords
- CD25+, Tregs, DLI, Donor lymphocyte infusion
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CliniMACS CD25 Reagent DeviceDevice
Used to engineer CD25+ depleted donor lymphocytes which will be infused intravenously over 5-10 minutes
| Study group | Role | What they receive |
|---|---|---|
| CD25+ Treg depleted DLI dose schema | Experimental | Patients will receive a defined dose of CD25+ Treg depleted DLI. 5 patients will be enrolled, initially at dose level B, and subsequent cohorts will be dose adjusted per the CD3+ dose escalation/de-escalation schema:
* Dose level -C: 3x10^7 (CD3+Dose (#cells/kg*))
* Dose level -B: 1x10^7 (CD3+Dose (#cells/kg*))
* Dose level -A: 1x10^6 (CD3+Dose (#cells/kg*)) *Recipient's body weight in Kg Receives: Device: CliniMACS CD25 Reagent Device |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the feasibility of using the ClinMACS CD25 Reagent device to engineer a DLI product outlined in the protocol
Measured: 3 years
To determine the safety of CD25+ Treg depleted DLI in this patient population.
Measured: 3 years
Secondary outcomes (2)
To assess clinical response after infusions of CD25+ Treg depleted donor lymphocytes
Measured: 3 years
To assess the immunologic impact of infusions of CD25+ Treg depleted donor lymphocytes
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2008 (estimated)
- Study startDec 2007
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Responsible party
- Principal investigator, John Koreth, MD, Dana-Farber Cancer Institute
- Investigators
- John Koreth, MBBS, DPhil, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00675831
- Sponsor's protocol ID
- 07-193
- Status last verified
- Sep 2016
- First submitted
- 8 May 2008
- Last updated
- 29 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nikiforow S, Kim HT, Daley H, Reynolds C, Jones KT, Armand P, Ho VT, Alyea EP 3rd, Cutler CS, Ritz J, Antin JH, Soiffer RJ, Koreth J. A phase I study of CD25/regulatory T-cell-depleted donor lymphocyte infusion for relapse after allogeneic stem cell transplantation. Haematologica. 2016 Oct;101(10):1251-1259. doi: 10.3324/haematol.2015.141176. Epub 2016 Jun 27.
PubMed 27354021
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infusion of Donor Lymphocytes Depleted of CD25+ Regulatory T-cells in Patients With Relapsed Hematologic Malignancies After Matched Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00675831
- Acronym / sponsor ID
- 07-193
- Conditions
- Hematologic Malignancies
- Keywords
- CD25+, Tregs, DLI, Donor lymphocyte infusion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Study start
- Dec 2007
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 12 May 2008 (estimated)
- Results
- Not posted in the source record
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 this research study is to evaluate the safety and efficacy of cell depletion in a donor lymphocyte infusion (DLI) product with the use of the CliniMACS machine. Previously, patients with hematologic malignancies who have relapsed after transplant have been given infusions of donor white blood cells calsed donor lymphocyte infusion (DLI) as a way to boost their immune function and fight cancer. Information from other research studies suggests that lowering the number of a certain type of white blood cell called CD25+ Tregs in the DLI may allow for a greater effect. In this research study, we are looking for the appropriate dose of DLI depleted of the CD25+ Treg white blood cells that can be given safely.
Detailed description
- The original marrow/stem cell donor will undergo one or two white blood cell collection procedures called leukopheresis. The cells collected from the first leukopheresis will be sent to the laboratory where the amount of white blood cells collected will be measured. If the number of cells collected at the first leukopheresis is not enough, the donor will have a second leukopheresis procedure.
- Once enough lymphocytes are collected from the donor, the CliniMACS CD25 Reagent System device will reduce the number of CD25+ Tregs. The CD25+ depleted donor lymphocytes will then be infused to the participant intravenously. Participants will be observed for about one hour after the infusion.
- One, two, four and eight weeks after the DLI, participants will return to the clinic for follow-up visits. At each visit a physical exam, questions about the participants general health, and blood tests will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD25+ Treg depleted DLI dose schema | Experimental | Device: CliniMACS CD25 Reagent DevicePatients will receive a defined dose of CD25+ Treg depleted DLI. 5 patients will be enrolled, initially at dose level B, and subsequent cohorts will be dose adjusted per the CD3+ dose escalation/de-escalation schema: * Dose level -C: 3x10^7 (CD3+Dose (#cells/kg*)) * Dose level -B: 1x10^7 (CD3+Dose (#cells/kg*)) * Dose level -A: 1x10^6 (CD3+Dose (#cells/kg*)) *Recipient's body weight in Kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with hematologic malignancies that have relapsed after HLA-A, -B, -C, and-DRBI matched allogeneic hematopoietic stem cell transplantation
- At least 2 months following hematopoietic stem cell transplantation
- Off any systemic immunosuppressive medication for treatment or prevention of GVHD, for a minimum of 2 weeks prior to study entry
- Recipient with donor chimerism of 20% or greater within 6 weeks prior to DLI
- Patient with less than 50% bone marrow involvement (% cellularity) and less than 5cm lymph nodes, in the 6 weeks prior to DLI
Key exclusion criteria (6 listed)
- Relapsed CML in chronic phase
- Prior donor lymphocyte infusion or other immunotherapy treatment within 8 weeks prior to enrollment
- Chemotherapy within 4 weeks prior to enrollment
- Clinically significant and active autoimmune disease in donor or patient. This is defined as autoimmune disease resulting in organ dysfunction and/or requiring systemic therapy
- Evidence of active acute or chronic GVHD
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 |
|---|---|---|
| CliniMACS CD25 Reagent DeviceUsed to engineer CD25+ depleted donor lymphocytes which will be infused intravenously over 5-10 minutes | Device | CD25+ Treg depleted DLI dose schema |
Primary outcome
To determine the feasibility of using the ClinMACS CD25 Reagent device to engineer a DLI product outlined in the protocol
Time frame: 3 years
To determine the safety of CD25+ Treg depleted DLI in this patient population.
Time frame: 3 years
2 secondary outcomes
To assess clinical response after infusions of CD25+ Treg depleted donor lymphocytes
Time frame: 3 years
To assess the immunologic impact of infusions of CD25+ Treg depleted donor lymphocytes
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Derived from this study: PubMed 27354021Nikiforow S, Kim HT, Daley H, Reynolds C, Jones KT, Armand P, Ho VT, Alyea EP 3rd, Cutler CS, Ritz J, Antin JH, Soiffer RJ, Koreth J. A phase I study of CD25/regulatory T-cell-depleted donor lymphocyte infusion for relapse after allogeneic stem cell transplantation. Haematologica. 2016 Oct;101(10):1251-1259. doi: 10.3324/haematol.2015.141176. Epub 2016 Jun 27.
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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.
John Koreth, MBBS, DPhil principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CliniMACS CD25 Reagent Device in people with Hematologic Malignancies, run by Dana-Farber Cancer Institute at 1 site in United States.
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 8 inclusion and 6 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 29 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the feasibility of using the ClinMACS CD25 Reagent device to engineer a DLI product outlined in the protocol (time frame: 3 years). The study lists 2 primary outcomes in all. 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 NCT00675831, which also lists 1 linked publication.
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 29 Sep 2016.