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

NCT01220544 | Unknown Phase 1 DMC

• 1 other identifier: BELEHAPLO-1412001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• transplant related mortality

  1 year

• effectiveness

  2 years

• technical aspects of the cell separation procedure

  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.

  28 days

Study Arms (1)

HaploTransplant with NK cells

EXPERIMENTAL

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

Interventions

Haploidentical transplantation with donor NK cells BIOLOGICAL

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.

HaploTransplant with NK cells

Eligibility Criteria

• Age: 18 Years - 54 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with AML or ALL in first CR with the following high risk features:
• AML with aberration Del (5q) -5, del (7q) -7, t(9;22) or t(6;9), abn 3q, 9q, 11q, 20q, 21q, 17p;
• AML with a complex caryotype;
• secondary AML after previous chemo- or radiotherapy or MDS;
• 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:
• relapse after autologous transplantation
• primary chemotherapy refractory disease
• All patients must fulfill the following criteria:
• lack of a suitable HLA-identical family, unrelated or cord blood donor
• no active infection, no severe impairment of cardial, pulmonary, renal and hepatic function
• blast count in the marrow \< 30%
• informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• University of Leipzig: collaborator

Study Sites (2)

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

Berlin, State of Berlin, 12200, Germany

RECRUITING

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

Leipzig, 04103, Germany

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Transplantation, Haploidentical

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Transplantation, Homologous; Transplantation; Surgical Procedures, Operative

Study Officials

• Lutz Uharel, MD

  Charite University Medicine

  PRINCIPAL INVESTIGATOR

• Dietger Niederwieser, MD

  University of Leipzig

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lutz Uharek, MD

CONTACT

+49308445; lutz.uharek@charite.de

Birte Friedrichs, MD

CONTACT

+49308445; birte.friedrichs@charite.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 13, 2010
• First Posted: October 14, 2010
• Study Start: July 1, 2001
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2011
• Last Updated: October 14, 2010

Record last verified: 2010-10

Locations

DE (2)