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

Acute Myeloid Leukemias Clinical Trial

Official title:

Transplantation of Hematopoetic Stem Cells and Infusion of CD56+CD3- NK Cells From Haploidentical Donors for Patients With Hematological Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01220544
• Other study ID #: BELEHAPLO-1412001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: October 13, 2010
• Last updated: October 13, 2010
• Start date: July 2001
• Est. completion date: October 2011

Study information

• Verified date: October 2010
• Source: Charite University, Berlin, Germany
• Contact: Lutz Uharek, MD
• Phone: +49308445
• Email: lutz.uharek[@]charite.de
• Is FDA regulated: No
• Health authority: Germany: State Office of Health and Social Affairs
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 54 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
Germany	Charite Campus Benjamin FRanklin, Medical Clinic III, Department of Hematology/Oncology	Berlin
Germany	Medical Clinic II, Department of Hematology/Oncology, University of Leipzig	Leipzig

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	University of Leipzig

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 year	Yes
Secondary	transplant related mortality	The investigation of transplant related mortality (incidence of veno occlusive disease; incidence and type of infectious complications).	1 year	No
Secondary	effectiveness	To evaluate the effectiveness of the therapy (relapse rate; disease free survival; MRD monitoring).	2 years	No
Secondary	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).	7 days	No
Secondary	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.	28 days	No