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

Phase 1

• Conditions: Advanced Hematological Malignancies; Indication for Allogeneic Stem Cell Transplantation; Acute Myeloid Leukemias; no HLA-identical Donor Available
• Interventions: Biological: Haploidentical transplantation with donor NK cells

• Registration Number: NCT01220544
• Lead Sponsor: Charite University, Berlin, Germany

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2001-07
• Status Verified: 2010-10
• Primary Completion: 2010-10
• Study First Submitted: 2010-10-13
• Study First Submitted QC: 2010-10-13
• Last Update Submitted: 2010-10-13
• Study First Posted: 2010-10-14
• Last Update Posted: 2010-10-14
• Study Completion: 2011-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HaploTransplant with NK cells	Haploidentical transplantation with donor NK cells	Haploidentical transplantation of mega-dose CD34+ hematopoetic stem cells with transfer of CD56+CD3-NK cells at day +2

Primary Outcome Measures

Name	Time	Method
To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation	1 year	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

Name	Time	Method
effectiveness	2 years	To evaluate the effectiveness of the therapy (relapse rate; disease free survival; MRD monitoring).
transplant related mortality	1 year	The investigation of transplant related mortality (incidence of veno occlusive disease; incidence and type of infectious complications).
technical aspects of the cell separation procedure	7 days	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.	28 days	Graft rejection is defined as neutrophils \< 0.5 x 10e9/l on day+28 post transplantation.

Trial Locations

Locations (2)

Charite Campus Benjamin FRanklin, Medical Clinic III, Department of Hematology/Oncology; 🇩🇪 Berlin, Germany

Medical Clinic II, Department of Hematology/Oncology, University of Leipzig; 🇩🇪 Leipzig, Germany