Back to resultsHaploidentical Transplantation With Early Adoptive Transfer of CD56+CD3- NK Cells
Primary Purpose
Acute Myeloid Leukemias, Advanced Hematological Malignancies, Indication for Allogeneic Stem Cell Transplantation
Status
Unknown status
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Haploidentical transplantation with donor NK cells
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemias
Eligibility Criteria
Inclusion Criteria: 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 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 Exclusion Criteria: 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
Sites / Locations
- Charite Campus Benjamin FRanklin, Medical Clinic III, Department of Hematology/OncologyRecruiting
- Medical Clinic II, Department of Hematology/Oncology, University of LeipzigRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
HaploTransplant with NK cells
Arm Description
Haploidentical transplantation of mega-dose CD34+ hematopoetic stem cells with transfer of CD56+CD3-NK cells at day +2
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
transplant related mortality
The investigation of transplant related mortality (incidence of veno occlusive disease; incidence and type of infectious complications).
effectiveness
To evaluate the effectiveness of the therapy (relapse rate; disease free survival; MRD monitoring).
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).
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.
Full Information
NCT ID
NCT01220544
First Posted
October 13, 2010
Last Updated
October 13, 2010
Sponsor
Charite University, Berlin, Germany
Collaborators
University of Leipzig
1. Study Identification
Unique Protocol Identification Number
NCT01220544
Brief Title
Haploidentical Transplantation With Early Adoptive Transfer of CD56+CD3- NK Cells
Official Title
Transplantation of Hematopoetic Stem Cells and Infusion of CD56+CD3- NK Cells From Haploidentical Donors for Patients With Hematological Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
October 2010
Overall Recruitment Status
Unknown status
Study Start Date
July 2001 (undefined)
Primary Completion Date
October 2010 (Anticipated)
Study Completion Date
October 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Charite University, Berlin, Germany
Collaborators
University of Leipzig
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemias, Advanced Hematological Malignancies, Indication for Allogeneic Stem Cell Transplantation, no HLA-identical Donor Available
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HaploTransplant with NK cells
Arm Type
Experimental
Arm Description
Haploidentical transplantation of mega-dose CD34+ hematopoetic stem cells with transfer of CD56+CD3-NK cells at day +2
Intervention Type
Biological
Intervention Name(s)
Haploidentical transplantation with donor NK cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
transplant related mortality
Description
The investigation of transplant related mortality (incidence of veno occlusive disease; incidence and type of infectious complications).
Time Frame
1 year
Title
effectiveness
Description
To evaluate the effectiveness of the therapy (relapse rate; disease free survival; MRD monitoring).
Time Frame
2 years
Title
technical aspects of the cell separation procedure
Description
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).
Time Frame
7 days
Title
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.
Description
Graft rejection is defined as neutrophils < 0.5 x 10e9/l on day+28 post transplantation.
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
54 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lutz Uharek, MD
Phone
+49308445
Ext
4550
Email
lutz.uharek@charite.de
First Name & Middle Initial & Last Name or Official Title & Degree
Birte Friedrichs, MD
Phone
+49308445
Ext
4574
Email
birte.friedrichs@charite.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lutz Uharel, MD
Organizational Affiliation
Charite University Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dietger Niederwieser, MD
Organizational Affiliation
University of Leipzig
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charite Campus Benjamin FRanklin, Medical Clinic III, Department of Hematology/Oncology
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lutz Uharek, Prof.
Phone
+49308445
Ext
4550
Email
lutz.uharek@charite.de
First Name & Middle Initial & Last Name & Degree
Birte Friedrichs, Dr.
Phone
+49308445
Ext
4574
Email
birte.friedrichs@charite.de
Facility Name
Medical Clinic II, Department of Hematology/Oncology, University of Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dietger Niederwieser, Prof.
Phone
+4934197
Ext
13050
Email
dietger@medizin.uni-leipzig.de
First Name & Middle Initial & Last Name & Degree
Nadezda Basara, Dr.
Email
Nadezda.Basara@medizin.uni-leipzig.de
12. IPD Sharing Statement
Learn more about this trial
Haploidentical Transplantation With Early Adoptive Transfer of CD56+CD3- NK Cells
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