Acute Myeloid LeukemiasPhase 1/2NCT01220544
Haploidentical Transplantation With Early Adoptive Transfer of CD56+CD3- NK Cells
A Phase 1/2 study testing Haploidentical transplantation with donor NK cells in people with Acute Myeloid Leukemias and Advanced Hematological Malignancies, run by Charite University, Berlin, Germany at 2 sites in Germany.
Trial summary
Experimental and clinical data suggest that alloreactive NK cells can reduce the risk of graft-rejection, GvHD and leukemic relapse after HLA-mismatched transplantation. The effectiveness of allogeneic NK cells is a function of HLA-differences between donor and recipient that give rise to NK cell clones which do not… Read more about this study
- Who is it for?
- Ages 18 to 54 years
- Conditions the study is for
- Acute Myeloid Leukemias, Advanced Hematological Malignancies, Indication for Allogeneic Stem Cell Transplantation
- What is being tested?
- Haploidentical transplantation with donor NK cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesGermany
- Study dates
- Jul 2001to Oct 2011
- Phase
- Phase 1/2
- 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 54 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients with AML or ALL in first CR with the following high risk features:
- AML with aberration Del (5q) -5, del (7q) -7, t(9;22) or t(6;9), abn 3q, 9q, 11q, 20q, 21q, 17p;
- AML with a complex caryotype;
- secondary AML after previous chemo- or radiotherapy or MDS;
- Ph-positive ALL
- Patients with AML or ALL after induction failure or in second CR
Show all 15Show fewer
- Patients with CML in second chronic or accelerated phase
- Patients with malignant Lymphoma and the following high risk features:
- relapse after autologous transplantation
- primary chemotherapy refractory disease
- All patients must fulfill the following criteria:
- lack of a suitable HLA-identical family, unrelated or cord blood donor
- no active infection, no severe impairment of cardial, pulmonary, renal and hepatic function
- blast count in the marrow < 30%
- informed consent
Who cannot join
- active infection, no severe impairment of cardial, pulmonary, renal and hepatic function
- blast count in the marrow > 30%
- unable or unwilling to sign and/or understand informed consent
Trial locations and contacts
2 sites in 1 country.
Germany2 sites, 2 recruiting
- Recruiting
Charite Campus Benjamin FRanklin, Medical Clinic III, Department of Hematology/Oncology
Berlin, State of Berlin, 12200
Lutz Uharek, Prof., +49308445 ext. 4550, lutz.uharek@charite.de
Birte Friedrichs, Dr., +49308445 ext. 4574, birte.friedrichs@charite.de
- Recruiting
Medical Clinic II, Department of Hematology/Oncology, University of Leipzig
Leipzig, 04103
Dietger Niederwieser, Prof., +4934197 ext. 13050, dietger@medizin.uni-leipzig.de
Nadezda Basara, Dr., Nadezda.Basara@medizin.uni-leipzig.de
About this study
Official title: Transplantation of Hematopoetic Stem Cells and Infusion of CD56+CD3- NK Cells From Haploidentical Donors for Patients With Hematological Malignancies
Experimental and clinical data suggest that alloreactive NK cells can reduce the risk of graft-rejection, GvHD and leukemic relapse after HLA-mismatched transplantation. The effectiveness of allogeneic NK cells is a function of HLA-differences between donor and recipient that give rise to NK cell clones which do not express inhibitory receptors matching for the HLA molecules of the recipient. Aim of the study is to evaluate cellular therapy with alloreactive, IL-2 activated NK cells after transplantation of T-cell depleted stem cell grafts from one haplotype mismatched family donors in patients with hematological malignancies.
- Conditions
- Acute Myeloid Leukemias, Advanced Hematological Malignancies, Indication for Allogeneic Stem Cell Transplantation, no HLA-identical Donor Available
- Being tested
- Haploidentical transplantation with donor NK cells
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haploidentical transplantation with donor NK cellsBiological
Pat received a myeloablative conditioning regimen with 12 Gy total-body irradiation in six single doses from day -11 to day -9, thiotepa (5mg/kg/d) on days -8 and -7, fludarabine (40mg/m2/d) from day -6 to day -3, and OKT-3 (5mg/d) from day -5 to day +3. The stem cell graft was aimed to contain > 8 x 10e6 CD34+ cells/kg and < 5 x 10e4 CD3+ cells/kg. A minimum of 1 x 10e7 CD56+CD3- NK cells/kg will be transferred on days +2.
| Study group | Role | What they receive |
|---|---|---|
| HaploTransplant with NK cells | Experimental | Haploidentical transplantation of mega-dose CD34+ hematopoetic stem cells with transfer of CD56+CD3-NK cells at day +2 Receives: Biological: Haploidentical transplantation with donor NK cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation
To evaluate feasibility and safety of cellular immunotherapy with purified alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched hematopoietic stem cell transplantation in patients with high risk hematological malignancies who lack an HLA-identical donor.
Measured: 1 year
Secondary outcomes (4)
transplant related mortality
The investigation of transplant related mortality (incidence of veno occlusive disease; incidence and type of infectious complications).
Measured: 1 year
effectiveness
To evaluate the effectiveness of the therapy (relapse rate; disease free survival; MRD monitoring).
Measured: 2 years
technical aspects of the cell separation procedure
To investigate technical aspects of the cell separation procedure (problems of stem cell mobilization; yield, viability, sterility and purity of the CD34+ and CD56+CD3- cell fraction; log CD3 depletion; in vitro anti-leukemic activity of the CD56+CD3- cell fraction).
Measured: 7 days
stable engraftment of haploidentical stem cell grafts can be achieved after conditioning with total body irradiation, thiotepa, fludarabine and OKT3 and subsequent transfer of megadoses of positively selected CD34+ stem cells and CD56+CD3- NK-cells.
Graft rejection is defined as neutrophils < 0.5 x 10e9/l on day+28 post transplantation.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2010 (estimated)
- Study startJul 2001
- Primary completionOct 2010 (estimated)
- Study completionOct 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiasStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- University of Leipzig
- Investigators
- Lutz Uharel, MD, Principal investigator, Charite University MedicineDietger Niederwieser, MD, Principal investigator, University of Leipzig
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01220544
- Sponsor's protocol ID
- BELEHAPLO-1412001
- Status last verified
- Oct 2010
- First submitted
- 13 Oct 2010
- Last updated
- 14 Oct 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transplantation of Hematopoetic Stem Cells and Infusion of CD56+CD3- NK Cells From Haploidentical Donors for Patients With Hematological Malignancies
- ClinicalTrials.gov ID
- NCT01220544
- Acronym / sponsor ID
- BELEHAPLO-1412001
- Conditions
- Acute Myeloid Leukemias, Advanced Hematological Malignancies, Indication for Allogeneic Stem Cell Transplantation, no HLA-identical Donor Available
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- University of Leipzig
- Study start
- Jul 2001
- Primary completion
- Oct 2010 (estimated)
- Study completion
- Oct 2011 (estimated)
- First posted
- 14 Oct 2010 (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.
Experimental and clinical data suggest that alloreactive NK cells can reduce the risk of graft-rejection, GvHD and leukemic relapse after HLA-mismatched transplantation. The effectiveness of allogeneic NK cells is a function of HLA-differences between donor and recipient that give rise to NK cell clones which do not express inhibitory receptors matching for the HLA molecules of the recipient. Aim of the study is to evaluate cellular therapy with alloreactive, IL-2 activated NK cells after transplantation of T-cell depleted stem cell grafts from one haplotype mismatched family donors in patients with hematological malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HaploTransplant with NK cells | Experimental | Biological: Haploidentical transplantation with donor NK cellsHaploidentical transplantation of mega-dose CD34+ hematopoetic stem cells with transfer of CD56+CD3-NK cells at day +2 |
Who may qualify
- Ages
- 18 to 54 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Patients with AML or ALL in first CR with the following high risk features:
- Patients with AML or ALL after induction failure or in second CR
- Patients with CML in second chronic or accelerated phase
- Patients with malignant Lymphoma and the following high risk features:
- All patients must fulfill the following criteria:
Key exclusion criteria (3 listed)
- active infection, no severe impairment of cardial, pulmonary, renal and hepatic function
- blast count in the marrow > 30%
- unable or unwilling to sign and/or understand informed consent
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 |
|---|---|---|
| Haploidentical transplantation with donor NK cellsPat received a myeloablative conditioning regimen with 12 Gy total-body irradiation in six single doses from day -11 to day -9, thiotepa (5mg/kg/d) on days -8 and -7, fludarabine (40mg/m2/d) from day -6 to day -3, and OKT-3 (5mg/d) from day -5 to day +3. The stem cell graft was aimed to contain > 8 x 10e6 CD34+ cells/kg and < 5 x 10e4 CD3+ cells/kg. A minimum of 1 x 10e7 CD56+CD3- NK cells/kg will be transferred on days +2. | Biological | HaploTransplant with NK cells |
Primary outcome
To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation
Time frame: 1 year
To evaluate feasibility and safety of cellular immunotherapy with purified alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched hematopoietic stem cell transplantation in patients with high risk hematological malignancies who lack an HLA-identical donor.
4 secondary outcomes
transplant related mortality
Time frame: 1 year
effectiveness
Time frame: 2 years
technical aspects of the cell separation procedure
Time frame: 7 days
stable engraftment of haploidentical stem cell grafts can be achieved after conditioning with total body irradiation, thiotepa, fludarabine and OKT3 and subsequent transfer of megadoses of positively selected CD34+ stem cells and CD56+CD3- NK-cells.
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2010.
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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.
Lutz Uharel, MD principal investigator
Charite University Medicine
Dietger Niederwieser, MD principal investigator
University of Leipzig
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Haploidentical transplantation with donor NK cells in people with Acute Myeloid Leukemias and Advanced Hematological Malignancies, run by Charite University, Berlin, Germany at 2 sites in Germany.
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 15 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 14 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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 combined 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.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lutz Uharek, MD (+49308445 ext. 4550, lutz.uharek@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation (time frame: 1 year). 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 14 Oct 2010.