Clinical trial NCT01220544: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemias
Advanced Hematological Malignancies
Indication for Allogeneic Stem Cell Transplantation
no HLA-identical Donor Available
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: University of Leipzig
First posted: 2010-10-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation
timeFrame: 1 year
Secondary outcomes:
measure: transplant related mortality
timeFrame: 1 year
measure: effectiveness
timeFrame: 2 years
measure: technical aspects of the cell separation procedure
timeFrame: 7 days
measure: 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.
timeFrame: 28 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite Campus Benjamin FRanklin, Medical Clinic III, Department of Hematology/Oncology
city: Leipzig
country: Germany
facility: Medical Clinic II, Department of Hematology/Oncology, University of Leipzig
Study officials:
affiliation: Charite University Medicine
name: Lutz Uharel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Leipzig
name: Dietger Niederwieser, MD
role: PRINCIPAL_INVESTIGATOR
References: