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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified December 2014 by University Hospital Tuebingen.
Recruitment status was:  Recruiting
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. med. Wolfgang Bethge, University Hospital Tuebingen
ClinicalTrials.gov Identifier:
NCT00961142
First received: August 17, 2009
Last updated: December 3, 2014
Last verified: December 2014
  Purpose
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

Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Drug: Fludarabine, Thiotepa, Melphalan, Thymoglobuline (ATG)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Phase II Study of Haploidentical Hematopoietic Cell Transplantation With CD3/CD19 Depleted Grafts After a Reduced Intensity Conditioning Regimen for Adult Patients With Acute Leukemia

Resource links provided by NLM:


Further study details as provided by University Hospital Tuebingen:

Primary Outcome Measures:
  • Evaluation of treatment related mortality after haploidentical HCT [ Time Frame: 1 year after HCT ] [ Designated as safety issue: Yes ]
    Cumulative Incidence of treatment related mortality


Secondary Outcome Measures:
  • overall survival [ Time Frame: 1, 2 and 5 years after inclusion ] [ Designated as safety issue: Yes ]
    by Kaplan-Meier

  • Evaluate Engraftment [ Time Frame: One year after HCT ] [ Designated as safety issue: Yes ]
  • Evaluate Toxicity [ Time Frame: One year after HCT ] [ Designated as safety issue: Yes ]
  • Evaluate Disease Free Survival [ Time Frame: 1, 2 and 5 years after inclusion ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: June 2009
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Fludarabine, Thiotepa, Melphalan, Thymoglobuline (ATG)
    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

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
    • Early or mature T-ALL
    • Initially refractory patients with late CR
    • Rising MRD level
    • Patients in 2. CR
    • Relapse after a preceding allogeneic HCT from an HLA-identical donor
    • No HLA-identical donor (not more than 1 antigen mismatch (9/10-Match) or more than 2 allelic mismatches by high-resolution typing). Critical cases should be discussed with the PI.
    • Age <=65, >=18 years
    • Karnofsky Index >60%

Exclusion Criteria:

  • 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
  • Patients with a history of psychiatric illness or condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction)
  • Patients unwilling or unable to comply with the protocol
  • Unable to give informed consent
  • Enrollment in an other trial interfering with the endpoints of this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00961142

Locations
Germany
University of Dresden Medical Center
Dresden, Germany, D-01307
Center for Marrow Transplantation, University of Essen
Essen, Germany, 45122
Medical Center University of Halle
Halle, Germany, 06120
Medical Center University of Hamburg
Hamburg, Germany, 20246
Medical Center University of Muenster
Muenster, Germany, 48149
South West German Cancer Center, University of Tuebingen Medical Center
Tuebingen, Germany, 72076
Deutsche Klinik für Diagnostik
Wiesbaden, Germany, 65191
University of Wuerzburg Medical Center
Wuerzburg, Germany, D-97070
Sponsors and Collaborators
University Hospital Tuebingen
Investigators
Principal Investigator: Wolfgang A. Bethge, MD Medical Center University Hospital Tuebingen
  More Information

Additional Information:
Publications:
Responsible Party: Prof. Dr. med. Wolfgang Bethge, Prof. Dr., University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT00961142     History of Changes
Other Study ID Numbers: EudraCT 2007-006016-33 
Study First Received: August 17, 2009
Last Updated: December 3, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by University Hospital Tuebingen:
Haploidentical Transplantation
CD3/CD19 Depletion
AML
ALL
Reduced Intensity Conditioning

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Fludarabine phosphate
Melphalan
Thiotepa
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on December 02, 2016