Haploidentical Stem Cell Transplantation With CD3/CD19 Depletion and Reduced Intensity Conditioning in Patients With Acute Leukemia

NCT00961142 | Terminated Phase 2 DMC

• 1 other identifier: EudraCT 2007-006016-33
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 8

Brief Summary

Feasibility and toxicity of haploidentical allogeneic HCT after a reduced intensity conditioning regimen with CD3/CD19 depleted grafts. This study enrolls patients with acute leukemia in complete remission with an indication for allogeneic HCT but without a suitable HLA-identical donor

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia

Keywords

Haploidentical Transplantation; CD3/CD19 Depletion; AML; ALL; Reduced Intensity Conditioning

Outcome Measures

Primary Outcomes (1)

• Evaluation of treatment related mortality after haploidentical HCT

  Cumulative Incidence of treatment related mortality

  1 year after HCT

Secondary Outcomes (4)

• overall survival

  1, 2 and 5 years after inclusion

• Evaluate Engraftment

  One year after HCT

• Evaluate Toxicity

  One year after HCT

• Evaluate Disease Free Survival

  1, 2 and 5 years after inclusion

Interventions

Fludarabine, Thiotepa, Melphalan, Thymoglobuline (ATG) DRUG

Conditioning with Fludarabine 30 mg/m2/24h day-8 to -4, Thiotepa 2x5 mg/kg day -3, Melphalan 60 mg/m2 day -2 to -1 and Thymoglobuline (ATG)1.5mg/kg/day day -9 to -6. PBSC depleted of CD3 and CD19 cells by immunomagnetic depletion on CliniMACS.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with either ALL or AML in CR with an indication for allogeneic HCT according to the following criteria:
• AML: high risk patients with one or more of the following risk factors:
• FLT-3 mutation
• Complex cytogenetics
• abn(3q), -5/5q-, -7/7q-, abn(12p), abn(17p)
• Late CR \> induction I
• Age \>60
• Patients in 2.CR
• Secondary AML
• Relapse after a preceding allogeneic HCT from an HLA-identical donor
• ALL: high risk patients with one or more of the following risk factors:
• Pro-B-ALL
• Initial WBC \>30.000/µL
• CR after day 46 after Induction II
• Complex cytogenetics, t(9,22), t(4,11)

You may not qualify if:

• Patients with \>5% blasts in BM at the time of transplantation
• Less than 3 months after preceding HCT
• CNS involvement with disease
• History of neurologic impairment such as: seizures, severe peripheral neuropathy, signs of leukoencephalopathy, CNS infection, multiple intrathecal chemotherapies, CNS irradiation. In case of heavy pretreatment with irradiation or intrathecal chemotherapy pretransplant CNS MRI and neurological consultation are mandatory
• Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month.
• Liver function abnormalities with bilirubin \>2 mg/dL and elevation of transaminases higher 2x upper limit of normal.
• Chronic active viral hepatitis
• Ejection fraction \<40 % on echocardiography
• Patients with \> grade II hypertension by CTC criteria
• Creatinine clearance \<50 ml/min
• Respiratory failure necessitating supplemental oxygen or DLCO \<30%
• Allergy against murine antibodies
• HIV-Infection
• Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control during study treatment and for at least 12 months thereafter. (Women of childbearing potential must have a negative serum pregnancy test at study entry)
• Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (8)

University of Dresden Medical Center

Dresden, D-01307, Germany

Location

Center for Marrow Transplantation, University of Essen

Essen, 45122, Germany

Location

Medical Center University of Halle

Halle, 06120, Germany

Location

Medical Center University of Hamburg

Hamburg, 20246, Germany

Location

Medical Center University of Muenster

Münster, 48149, Germany

Location

South West German Cancer Center, University of Tuebingen Medical Center

Tübingen, 72076, Germany

Location

Deutsche Klinik für Diagnostik

Wiesbaden, 65191, Germany

Location

University of Wuerzburg Medical Center

Würzburg, D-97070, Germany

Location

Related Publications (2)

• Bethge WA, Faul C, Bornhauser M, Stuhler G, Beelen DW, Lang P, Stelljes M, Vogel W, Hagele M, Handgretinger R, Kanz L. Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: an update. Blood Cells Mol Dis. 2008 Jan-Feb;40(1):13-9. doi: 10.1016/j.bcmd.2007.07.001. Epub 2007 Sep 14.

  PMID: 17869547 BACKGROUND

• Bethge WA, Haegele M, Faul C, Lang P, Schumm M, Bornhauser M, Handgretinger R, Kanz L. Haploidentical allogeneic hematopoietic cell transplantation in adults with reduced-intensity conditioning and CD3/CD19 depletion: fast engraftment and low toxicity. Exp Hematol. 2006 Dec;34(12):1746-52. doi: 10.1016/j.exphem.2006.08.009.

  PMID: 17157172 BACKGROUND

Related Links

• Homepage BMT-Study Group Tuebingen

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

fludarabine; Thiotepa; Melphalan; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Wolfgang A. Bethge, MD

  Medical Center University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: August 17, 2009
• First Posted: August 18, 2009
• Study Start: June 1, 2009
• Primary Completion: December 30, 2015
• Study Completion: December 30, 2015
• Last Updated: July 5, 2022

Record last verified: 2022-06

Locations

DE (8)