Graft Versus Host DiseasePhase 1NCT00725062
Donor T Cells in Treating Patients With High-Risk Hematologic Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant
A Phase 1 study testing CD4+CD25+ regulatory T cells and allogeneic hematopoietic stem cell transplantation in people with Graft Versus Host Disease and Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Graft Versus Host Disease, Leukemia, Lymphoma
- What is being tested?
- CD4+CD25+ regulatory T cells and allogeneic hematopoietic stem cell transplantation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Apr 2010
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of a high-risk hematologic malignancy, including any of the following:
- Acute lymphocytic leukemia
- Acute myelocytic leukemia
- Chronic myelogenous leukemia
- Myelodysplastic syndrome
- Non-Hodgkin lymphoma
Show all 16Show fewer
- Multiple myeloma
- Meet eligibility criteria and co-enrolled in one of the following University of Minnesota protocols:
- MT2001-02 consisting of myeloablative prep (cyclophosphamide and total body irradiation) followed by HLA-identical sibling peripheral blood progenitor cells (PBPC) transplantation
- MT2001-10 consisting of nonmyeloablative prep (cyclophosphamide, fludarabine and total body irradiation) followed by HLA-identical sibling PBPC transplantation
- Voluntarily written informed consent
- Must have an HLA-identical sibling donor available, meeting the following criteria:
- 12 to 75 years of age, >40 kg body weight and in good health
- Matched to recipient for HLA-A, B,DRB1 identical sibling match to recipient
- Must be able and willing to have a separate apheresis collection performed on day -21 for the purposes of this study (in addition to the apheresis required for the transplant protocol)
- Human immunodeficiency virus nucleic acid testing (HIV-NAT) negative, Human T-lymphotropic virus 1 (HTLV-1), HTLV-2 negative, hepatitic B and C negative
Who cannot join
- Not pregnant or nursing
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation
RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of donor T cells may helps stop the patient's immune system from rejecting the donor's stem cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of donor T cells in treating patients with high-risk hematologic cancer who are undergoing donor peripheral blood stem cell transplant.
Note: Only Phase I portion of study was performed. Due to slow accrual, study was closed before Phase II portion of study.
Read the detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose (MTD) of CD4+/CD25+ cells that can be safely administered to patients undergoing HLA-identical sibling donor Peripheral Blood Progenitor Cell (PBPC) transplantation.
- To determine whether CD4+ and CD25+ cells can be safely administered to patients with high-risk hematologic malignancies undergoing HLA-identical sibling donor PBPC transplantation.
Secondary
- To determine the incidence of grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, relapse, and survival after administration of CD4+ and CD25+ regulatory T cells in these patients.
OUTLINE: This is a dose-escalation study of CD4+ and CD25+ donor regulatory T cells followed by a phase II study. All patients receive myeloablative preparative therapy and GVHD prophylaxis as per University of Minnesota protocol UMN-MT2001-02 or UMN-MT2001-10.
- First allogeneic peripheral blood progenitor cell (PBPC) infusion: Patients receive unmobilized, culture-expanded, CD4- and CD25-positive donor regulatory T cells IV over 15-60 minutes at the assigned dose on day -2.
- Second allogeneic PBPC infusion: Patients undergo matched-sibling donor PBPC transplantation IV on day 0.
Patients undergo blood sample collection prior to commencement of preparative therapy and then at day 100, 6 months, and 1 year after PBPC transplantation. Samples are analyzed for immune reconstitution by immunophenotyping and functional analyses.
After completion of study therapy, patients are followed for up to 1 year.
- Conditions
- Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Being tested
- CD4+CD25+ regulatory T cells, allogeneic hematopoietic stem cell transplantation
- Keywords
- graft versus host disease, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma
- Medical subject headings
- Graft vs Host Disease, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD4+CD25+ regulatory T cellsBiological
Cohort 1 will receive 3 x 10^6 CD4+CD25+ cells/kg, Cohort 2 will receive 1 x 10^7 CD4+CD25+ cells/kg, Cohort 3 will receive 3 x 10^7 CD4+CD25 cells/kg
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Also called peripheral blood progenitor cell (PBPC) transplantation
Occurs on Day 0 of study - HLA-identical sibling donor peripheral blood progenitor cell (PBPC) transplantation
| Study group | Role | What they receive |
|---|---|---|
| Patients Receiving CD4+/CD25+ cells | Experimental | CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant) Receives: Biological: CD4+CD25+ regulatory T cells; Procedure: allogeneic hematopoietic stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)
Measured: Day 0 (48 hours post infusion)
Incidence of grade 3-5 infusional toxicity (phase II)
Measured: Day 0 (48 hours post infusion)
Secondary outcomes (5)
Cumulative incidence of grade II-IV acute graft-versus-host-disease (GVHD)
Measured: Day 100 Post Infusion
Incidence of chronic graft-versus-host disease (GVHD)
Measured: Month 6 Post Infusion
Incidence of Relapse
Measured: Month 6 Post Infusion
Overall Survival
Measured: Day 100 and 1 Year Post Infusion
Disease-free survival
Measured: Day 100 and 1 Year Post Infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2008 (estimated)
- Study startJun 2008
- Primary completionApr 2010
- Study completionApr 2010
Why it stopped: Slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Margaret L. MacMillan, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00725062
- Sponsor's protocol ID
- 2004LS034
- Other IDs
- MT2004-03
- Status last verified
- Nov 2017
- First submitted
- 29 Jul 2008
- Last updated
- 29 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation
- ClinicalTrials.gov ID
- NCT00725062
- Acronym / sponsor ID
- 2004LS034
- Conditions
- Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Keywords
- graft versus host disease, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 30 Jul 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.
RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of donor T cells may helps stop the patient's immune system from rejecting the donor's stem cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of donor T cells in treating patients with high-risk hematologic cancer who are undergoing donor peripheral blood stem cell transplant.
Note: Only Phase I portion of study was performed. Due to slow accrual, study was closed before Phase II portion of study.
Detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose (MTD) of CD4+/CD25+ cells that can be safely administered to patients undergoing HLA-identical sibling donor Peripheral Blood Progenitor Cell (PBPC) transplantation.
- To determine whether CD4+ and CD25+ cells can be safely administered to patients with high-risk hematologic malignancies undergoing HLA-identical sibling donor PBPC transplantation.
Secondary
- To determine the incidence of grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, relapse, and survival after administration of CD4+ and CD25+ regulatory T cells in these patients.
OUTLINE: This is a dose-escalation study of CD4+ and CD25+ donor regulatory T cells followed by a phase II study. All patients receive myeloablative preparative therapy and GVHD prophylaxis as per University of Minnesota protocol UMN-MT2001-02 or UMN-MT2001-10.
- First allogeneic peripheral blood progenitor cell (PBPC) infusion: Patients receive unmobilized, culture-expanded, CD4- and CD25-positive donor regulatory T cells IV over 15-60 minutes at the assigned dose on day -2.
- Second allogeneic PBPC infusion: Patients undergo matched-sibling donor PBPC transplantation IV on day 0.
Patients undergo blood sample collection prior to commencement of preparative therapy and then at day 100, 6 months, and 1 year after PBPC transplantation. Samples are analyzed for immune reconstitution by immunophenotyping and functional analyses.
After completion of study therapy, patients are followed for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients Receiving CD4+/CD25+ cells | Experimental | Biological: CD4+CD25+ regulatory T cells, Procedure: allogeneic hematopoietic stem cell transplantationCD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Diagnosis of a high-risk hematologic malignancy, including any of the following:
- Meet eligibility criteria and co-enrolled in one of the following University of Minnesota protocols:
- Voluntarily written informed consent
- Must have an HLA-identical sibling donor available, meeting the following criteria:
Key exclusion criteria (1 listed)
- Not pregnant or nursing
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 |
|---|---|---|
| CD4+CD25+ regulatory T cellsCohort 1 will receive 3 x 10^6 CD4+CD25+ cells/kg, Cohort 2 will receive 1 x 10^7 CD4+CD25+ cells/kg, Cohort 3 will receive 3 x 10^7 CD4+CD25 cells/kg | Biological | Patients Receiving CD4+/CD25+ cells |
| allogeneic hematopoietic stem cell transplantationAlso: peripheral blood progenitor cell (PBPC) transplantationOccurs on Day 0 of study - HLA-identical sibling donor peripheral blood progenitor cell (PBPC) transplantation | Procedure or surgery | Patients Receiving CD4+/CD25+ cells |
Primary outcome
Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)
Time frame: Day 0 (48 hours post infusion)
Incidence of grade 3-5 infusional toxicity (phase II)
Time frame: Day 0 (48 hours post infusion)
5 secondary outcomes
Cumulative incidence of grade II-IV acute graft-versus-host-disease (GVHD)
Time frame: Day 100 Post Infusion
Incidence of chronic graft-versus-host disease (GVHD)
Time frame: Month 6 Post Infusion
Incidence of Relapse
Time frame: Month 6 Post Infusion
Overall Survival
Time frame: Day 100 and 1 Year Post Infusion
Disease-free survival
Time frame: Day 100 and 1 Year Post Infusion
Results and safety
The study was stopped early (reason given: Slow accrual.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2017.
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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.
Margaret L. MacMillan, MD principal investigator
Masonic Cancer Center, University of Minnesota
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 CD4+CD25+ regulatory T cells and allogeneic hematopoietic stem cell transplantation in people with Graft Versus Host Disease and Leukemia, run by Masonic Cancer Center, University of Minnesota 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 16 inclusion and 1 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: stopped early, as of the sponsor's last update on 29 Nov 2017. 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 was stopped early (reason given: Slow accrual.). Results are not available in the source record.
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?
Maximum tolerated dose of CD4+CD25+ cells/kg (phase I) (time frame: Day 0 (48 hours post infusion)). 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?
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 Nov 2017.