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

NCT ID: NCT01220544

Last Updated: 2010-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-07-31

Study Completion Date

2011-10-31

Brief Summary

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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

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Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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HaploTransplant with NK cells

Haploidentical transplantation of mega-dose CD34+ hematopoetic stem cells with transfer of CD56+CD3-NK cells at day +2

Group Type EXPERIMENTAL

Haploidentical transplantation with donor NK cells

Intervention Type 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.

Interventions

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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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

54 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Leipzig

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role lead

Responsible Party

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Charite University Medicine

Principal Investigators

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Lutz Uharel, MD

Role: PRINCIPAL_INVESTIGATOR

Charite University Medicine

Dietger Niederwieser, MD

Role: PRINCIPAL_INVESTIGATOR

University of Leipzig

Locations

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

Berlin, State of Berlin, Germany

Site Status RECRUITING

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

Leipzig, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Lutz Uharek, MD

Role: CONTACT

+49308445 ext. 4550

Birte Friedrichs, MD

Role: CONTACT

+49308445 ext. 4574

Facility Contacts

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Lutz Uharek, Prof.

Role: primary

+49308445 ext. 4550

Birte Friedrichs, Dr.

Role: backup

+49308445 ext. 4574

Dietger Niederwieser, Prof.

Role: primary

+4934197 ext. 13050

Nadezda Basara, Dr.

Role: backup

Other Identifiers

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BELEHAPLO-1412001

Identifier Type: -

Identifier Source: org_study_id