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

Phase 2UnknownNCT01220544

Charite University, Berlin, Germany30 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemias Advanced Hematological Malignancies Indication for Allogeneic Stem Cell Transplantation no HLA-identical Donor Available

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 54 Years

Medical Language ↔ Plain English

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

Locations (2)

Charite Campus Benjamin FRanklin, Medical Clinic III, Department of Hematology/Oncology

Berlin, State of Berlin, Germany

RECRUITING

Medical Clinic II, Department of Hematology/Oncology, University of Leipzig

Leipzig, Germany

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 1 year

Secondary Outcomes

transplant related mortality

The investigation of transplant related mortality (incidence of veno occlusive disease; incidence and type of infectious complications).

Time frame: 1 year

effectiveness

To evaluate the effectiveness of the therapy (relapse rate; disease free survival; MRD monitoring).

Time frame: 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).

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.

Graft rejection is defined as neutrophils \< 0.5 x 10e9/l on day+28 post transplantation.

Time frame: 28 days