Leukemia, MyeloidPhase 3NCT00306332
T-cell and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation
A Phase 3 study testing T-cell and B-cell depletion in people with Leukemia, Myeloid and Leukemia, Lymphocytic, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
T-cell and B-cell depletion in allogeneic peripheral blood stem cell transplantation by using immunomagnetic negative and positive selection procedures Background: Removal of T-cells from the donor graft (T-cell depletion) offers the possibility for prevention of GVHD and subsequently less transplant related morbidity… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Leukemia, Myeloid, Leukemia, Lymphocytic, Myelodysplastic Syndrome
- What is being tested?
- T-cell and B-cell depletion
- Type of treatment
- Surgery or procedure
- How many people
- 250 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2006to not given
- Phase
- Phase 3
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with the diagnosis of:
- De novo acute myeloid leukaemia in first or second remission.
- Secondary acute myeloid leukaemia in first or second remission supervening after myelodysplastic syndrome or cytotoxic / immunosuppressive therapy.
- Acute lymphoblastic leukaemia in first or second remission.
- Myelodysplastic syndrome.
- Chronic myeloid leukaemia, patients who are candidate for SCT.
Show all 13Show fewer
- Malignant lymphoma following relapse or first line therapy resistant.
- Aggressive mantle cell lymphoma in first complete remission.
- Age 18-65 years.
- WHO performance 0-1 (see appendix ).
- Availability of an HLA-identical sibling or HLA, A, B, DRB, DQB -identical VUD donor.
- Life expectancy > 3 months.
- Witnessed written informed consent.
Who cannot join
- Patients with severe cardiac dysfunction (NYHA-classification II-IV)
- Patients with severe pulmonary dysfunction (vital capacity or diffusion < 70% of predicted value).
- Patients with hepatic dysfunction, bilirubin or transaminases > 2.5 x upper normal limit
- Patients with renal dysfunction, serum creatinin > 150 umol/liter or clearance < 40 ml/minute.
- Patients with a history of moderate ore severe CNS disturbances and psychiatric problems.
- Prior treatment with chemotherapy, immunotherapy, radiation therapy or surgery within the last 3 weeks before entering the study.
Show all 10Show fewer
- Patients with active uncontrolled infections.
- Patients who are poor medical risks because of non malignant systemic disease.
- Patients with severe coagulopathy.
- Patients to be known HIV positive.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
476 Hematology, University Medical Centre St Radboud Nijmegen
Nijmegen, 6500 HB
About this study
Official title: T-cel and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation by Using Immunomagnetic Negative and Positive Selection Procedures
T-cell and B-cell depletion in allogeneic peripheral blood stem cell transplantation by using immunomagnetic negative and positive selection procedures
Background:
Read more
Removal of T-cells from the donor graft (T-cell depletion) offers the possibility for prevention of GVHD and subsequently less transplant related morbidity and mortality after allogeneic stem cell transplantation (SCT). There are several techniques to deplete T-cells from the stem cell grafts e.g. physical, immunological and combined physical / immunological separation methods. All these techniques result in a stem cell graft with sufficient CD34+ stem cells combined with an adequate depletion of T and B cells. CD34+ selected stem cell grafts are very pure and do not contain any additional cell populations. In contrast, CD3+/CD19+ depleted grafts still contain NK-cells, monocytes and dendritic cells that are part of the innate immune system. Theoretically,the presence of these cells may positively influence immunological reconstitution and the graft-versus-leukaemia (GVL) effect, respectively, resulting in improved outcome after SCT
Objectives:
To evaluate the differences in immunological reconstitution, transplant related mortality, disease-free survival and overall survival after T-cell depleted allogeneic SCT for haematological malignancies using either immunomagnetic CD34+ selection or immunomagnetic CD3+/CD19+ depletion using the CliniMACS system in approximately 270 consecutive patients.
Additionally in this study in 20 consecutive patients the kinetics of NK-cel reconstitution and differences in NK-cell repertoire will be monitored. NK-cell mediated anti-tumor reactivity will be monitored in patients transplanted with and without NK-cells in the stem cell graft (CD3+/CD19+ depletion, versus CD34+ selection). Secondary objectives are to evaluate the clinical relevance of minor histocompatibility-specific cytotoxic T-cell responses for the GVL effect, the kinetics of NK-cell reconstitution and differences in NK-cell repertoire using the different T-cell depletion protocols.
Design:
Single center prospective randomised phase III study
Population:
Patients eligible for allogeneic SCT according to the standard criteria of our institution who will receive an allogeneic T- and B-cell depleted SCT with peripheral stem cells of an HLA-identical sibling donor or an HLA-identical unrelated voluntary (VUD) donor.
Intervention:
T-cell depletion will be conducted using two different techniques: either immunomagnetic CD34+ selection or immunomagnetic CD3+/CD19+ depletion.
Endpoints:
Primary endpoints are immunological reconstitution, relapse, disease free survival and overall survival. Secondary endpoints: NK-cell reconstitution and NK-cell mediated anti-tumour reactivity. Cytotoxic T-cell responses for the GVL effect.
Estimated efforts and risks for participating patients:
We don't expect any extra patient efforts or risks because T-cell depletion is a standard procedure in our clinic for many years. There is extensive experience with immunological T-cell depletion techniques. We hypothesize CD3+/CD19+ depletion will favour stem cell transplant outcome. Immunological and molecular biological studies will be performed on blood samples already obtained as part of the standard protocol.
- Conditions
- Leukemia, Myeloid, Leukemia, Lymphocytic, Myelodysplastic Syndrome, Leukemia, Myeloid, Chronic, Lymphoma
- Being tested
- T-cell and B-cell depletion
- Keywords
- Allogeneic Stem cell transplantation, T-cell depletion, B-cell depletion, Immunomagnetic selection
- Medical subject headings
- Leukemia, Myeloid, Leukemia, Lymphoid, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T-cell and B-cell depletionProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
relapse
event-free survival
survival
Secondary outcomes (4)
clinical relevance of mHag-specific CTL responses for the GVL effect
Kinetics of NK-cel reconstitution
Differences in NK-cell repertoire
NK cell mediated anti tumor reactivity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2006 (estimated)
- Study startMar 2006
Why it stopped: Interim analysis has shown that the objectives of this study can not be reached
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Leukemia, MyeloidStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Nicolaas Schaap, MD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00306332
- Sponsor's protocol ID
- PSCT10
- Status last verified
- Aug 2009
- First submitted
- 22 Mar 2006
- Last updated
- 18 Aug 2009
- Results posted
- No
Publications
Schaap N, Schattenberg A, Bar B, Preijers F, Geurts van Kessel A, van der Maazen R, de Boo T, de Witte T. Outcome of transplantation for standard-risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen. Br J Haematol. 1997 Sep;98(3):750-9. doi: 10.1046/j.1365-2141.1997.d01-3499.x.
PubMed 9332335Schattenberg A, Schaap N, Preijers F, van der Maazen R, de Witte T. Outcome of T cell-depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients. Bone Marrow Transplant. 2000 Jul;26(1):17-22. doi: 10.1038/sj.bmt.1702451.
PubMed 10918401Schaap N, Schattenberg A, Bar B, Preijers F, van de Wiel van Kemenade E, de Witte T. Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions. Leukemia. 2001 Sep;15(9):1339-46. doi: 10.1038/sj.leu.2402203.
PubMed 11516094
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T-cel and B-cell Depletion in Allogeneic Peripheral Blood Stem Cell Transplantation by Using Immunomagnetic Negative and Positive Selection Procedures
- ClinicalTrials.gov ID
- NCT00306332
- Acronym / sponsor ID
- PSCT10
- Conditions
- Leukemia, Myeloid, Leukemia, Lymphocytic, Myelodysplastic Syndrome, Leukemia, Myeloid, Chronic, Lymphoma
- Keywords
- Allogeneic Stem cell transplantation, T-cell depletion, B-cell depletion, Immunomagnetic selection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim analysis has shown that the objectives of this study can not be reached
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Mar 2006
- First posted
- 23 Mar 2006 (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.
T-cell and B-cell depletion in allogeneic peripheral blood stem cell transplantation by using immunomagnetic negative and positive selection procedures
Background:
Removal of T-cells from the donor graft (T-cell depletion) offers the possibility for prevention of GVHD and subsequently less transplant related morbidity and mortality after allogeneic stem cell transplantation (SCT). There are several techniques to deplete T-cells from the stem cell grafts e.g. physical, immunological and combined physical / immunological separation methods. All these techniques result in a stem cell graft with sufficient CD34+ stem cells combined with an adequate depletion of T and B cells. CD34+ selected stem cell grafts are very pure and do not contain any additional cell populations. In contrast, CD3+/CD19+ depleted grafts still contain NK-cells, monocytes and dendritic cells that are part of the innate immune system. Theoretically,the presence of these cells may positively influence immunological reconstitution and the graft-versus-leukaemia (GVL) effect, respectively, resulting in improved outcome after SCT
Objectives:
To evaluate the differences in immunological reconstitution, transplant related mortality, disease-free survival and overall survival after T-cell depleted allogeneic SCT for haematological malignancies using either immunomagnetic CD34+ selection or immunomagnetic CD3+/CD19+ depletion using the CliniMACS system in approximately 270 consecutive patients.
Additionally in this study in 20 consecutive patients the kinetics of NK-cel reconstitution and differences in NK-cell repertoire will be monitored. NK-cell mediated anti-tumor reactivity will be monitored in patients transplanted with and without NK-cells in the stem cell graft (CD3+/CD19+ depletion, versus CD34+ selection). Secondary objectives are to evaluate the clinical relevance of minor histocompatibility-specific cytotoxic T-cell responses for the GVL effect, the kinetics of NK-cell reconstitution and differences in NK-cell repertoire using the different T-cell depletion protocols.
Design:
Single center prospective randomised phase III study
Population:
Patients eligible for allogeneic SCT according to the standard criteria of our institution who will receive an allogeneic T- and B-cell depleted SCT with peripheral stem cells of an HLA-identical sibling donor or an HLA-identical unrelated voluntary (VUD) donor.
Intervention:
T-cell depletion will be conducted using two different techniques: either immunomagnetic CD34+ selection or immunomagnetic CD3+/CD19+ depletion.
Endpoints:
Primary endpoints are immunological reconstitution, relapse, disease free survival and overall survival. Secondary endpoints: NK-cell reconstitution and NK-cell mediated anti-tumour reactivity. Cytotoxic T-cell responses for the GVL effect.
Estimated efforts and risks for participating patients:
We don't expect any extra patient efforts or risks because T-cell depletion is a standard procedure in our clinic for many years. There is extensive experience with immunological T-cell depletion techniques. We hypothesize CD3+/CD19+ depletion will favour stem cell transplant outcome. Immunological and molecular biological studies will be performed on blood samples already obtained as part of the standard protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with the diagnosis of:
- Age 18-65 years.
- WHO performance 0-1 (see appendix ).
- Availability of an HLA-identical sibling or HLA, A, B, DRB, DQB -identical VUD donor.
- Life expectancy > 3 months.
Key exclusion criteria (10 listed)
- Patients with severe cardiac dysfunction (NYHA-classification II-IV)
- Patients with severe pulmonary dysfunction (vital capacity or diffusion < 70% of predicted value).
- Patients with hepatic dysfunction, bilirubin or transaminases > 2.5 x upper normal limit
- Patients with renal dysfunction, serum creatinin > 150 umol/liter or clearance < 40 ml/minute.
- Patients with a history of moderate ore severe CNS disturbances and psychiatric problems.
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 |
|---|---|---|
| T-cell and B-cell depletion | Procedure or surgery | – |
Primary outcome
relapse
event-free survival
survival
4 secondary outcomes
clinical relevance of mHag-specific CTL responses for the GVL effect
Kinetics of NK-cel reconstitution
Differences in NK-cell repertoire
NK cell mediated anti tumor reactivity
Results and safety
The study was stopped early (reason given: Interim analysis has shown that the objectives of this study can not be reached). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2009.
- Background: PubMed 9332335Schaap N, Schattenberg A, Bar B, Preijers F, Geurts van Kessel A, van der Maazen R, de Boo T, de Witte T. Outcome of transplantation for standard-risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen. Br J Haematol. 1997 Sep;98(3):750-9. doi: 10.1046/j.1365-2141.1997.d01-3499.x.
- Background: PubMed 10918401Schattenberg A, Schaap N, Preijers F, van der Maazen R, de Witte T. Outcome of T cell-depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients. Bone Marrow Transplant. 2000 Jul;26(1):17-22. doi: 10.1038/sj.bmt.1702451.
- Background: PubMed 11516094Schaap N, Schattenberg A, Bar B, Preijers F, van de Wiel van Kemenade E, de Witte T. Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions. Leukemia. 2001 Sep;15(9):1339-46. doi: 10.1038/sj.leu.2402203.
Related trials for Leukemia, Myeloid
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
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.
Nicolaas Schaap, MD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing T-cell and B-cell depletion in people with Leukemia, Myeloid and Leukemia, Lymphocytic, run by Radboud University Medical Center at 1 site in Netherlands.
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 13 inclusion and 10 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 18 Aug 2009. 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 Netherlands. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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: Interim analysis has shown that the objectives of this study can not be reached). 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?
relapse. The study lists 3 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 NCT00306332, which also lists 3 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 18 Aug 2009.