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Haploidentical Transplantation With Early Adoptive Transfer of CD56+CD3- NK Cells

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by Charite University, Berlin, Germany.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
University of Leipzig
Information provided by:
Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01220544
First received: October 13, 2010
Last updated: NA
Last verified: October 2010
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemias
Advanced Hematological Malignancies
Indication for Allogeneic Stem Cell Transplantation
no HLA-identical Donor Available
 Biological: Haploidentical transplantation with donor NK cells
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transplantation of Hematopoetic Stem Cells and Infusion of CD56+CD3- NK Cells From Haploidentical Donors for Patients With Hematological Malignancies

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The investigation of transplant related mortality (incidence of veno occlusive disease; incidence and type of infectious complications).

  • effectiveness [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the effectiveness of the therapy (relapse rate; disease free survival; MRD monitoring).

  • technical aspects of the cell separation procedure [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    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. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Graft rejection is defined as neutrophils < 0.5 x 10e9/l on day+28 post transplantation.


Estimated Enrollment: 30
Study Start Date: July 2001
Estimated Study Completion Date: October 2011
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HaploTransplant with NK cells
Haploidentical transplantation of mega-dose CD34+ hematopoetic stem cells with transfer of CD56+CD3-NK cells at day +2
 Biological: Haploidentical transplantation with donor NK cells
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.

  Eligibility

Ages Eligible for Study:   18 Years to 54 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with AML or ALL in first CR with the following high risk features:

    1. AML with aberration Del (5q) -5, del (7q) -7, t(9;22) or t(6;9), abn 3q, 9q, 11q, 20q, 21q, 17p;
    2. AML with a complex caryotype;
    3. secondary AML after previous chemo- or radiotherapy or MDS;
    4. 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:

    1. relapse after autologous transplantation
    2. primary chemotherapy refractory disease

  • All patients must fulfill the following criteria:

    1. lack of a suitable HLA-identical family, unrelated or cord blood donor
    2. no active infection, no severe impairment of cardial, pulmonary, renal and hepatic function
    3. blast count in the marrow < 30%
    4. 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01220544

Contacts
Contact: Lutz Uharek, MD +49308445 ext 4550 lutz.uharek@charite.de
Contact: Birte Friedrichs, MD +49308445 ext 4574 birte.friedrichs@charite.de

Locations
Germany
Charite Campus Benjamin FRanklin, Medical Clinic III, Department of Hematology/Oncology Recruiting
Berlin, Germany, 12200
Contact: Lutz Uharek, Prof.     +49308445 ext 4550     lutz.uharek@charite.de    
Contact: Birte Friedrichs, Dr.     +49308445 ext 4574     birte.friedrichs@charite.de    
Medical Clinic II, Department of Hematology/Oncology, University of Leipzig Recruiting
Leipzig, Germany, 04103
Contact: Dietger Niederwieser, Prof.     +4934197 ext 13050     dietger@medizin.uni-leipzig.de    
Contact: Nadezda Basara, Dr.         Nadezda.Basara@medizin.uni-leipzig.de    
Sponsors and Collaborators
Charite University, Berlin, Germany
University of Leipzig
Investigators
Principal Investigator: Lutz Uharel, MD Charite University Medicine
Principal Investigator: Dietger Niederwieser, MD University of Leipzig
  More Information

No publications provided

Responsible Party: Prof. Dr. Lutz Uharek, Charite University Medicine
ClinicalTrials.gov Identifier: NCT01220544     History of Changes
Other Study ID Numbers: BELEHAPLO-1412001
Study First Received: October 13, 2010
Last Updated: October 13, 2010
Health Authority: Germany: State Office of Health and Social Affairs

Additional relevant MeSH terms:
Neoplasms
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
 Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on May 16, 2013