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

NCT ID: NCT00961142

Last Updated: 2022-07-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2015-12-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. med. Wolfgang Bethge

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wolfgang A. Bethge, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Center University Hospital Tuebingen

Locations

University of Dresden Medical Center

Dresden, , Germany

Center for Marrow Transplantation, University of Essen

Essen, , Germany

Medical Center University of Halle

Halle, , Germany

Medical Center University of Hamburg

Hamburg, , Germany

Medical Center University of Muenster

Münster, , Germany

South West German Cancer Center, University of Tuebingen Medical Center

Tübingen, , Germany

Deutsche Klinik für Diagnostik

Wiesbaden, , Germany

University of Wuerzburg Medical Center

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 17869547 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17157172 (View on PubMed)

Study Documents

Document Type: Results

View Document

Related Links

http://www.onkologie-tuebingen.de/ifa0.htm

Homepage BMT-Study Group Tuebingen

Other Identifiers

EudraCT 2007-006016-33

Identifier Type: -

Identifier Source: org_study_id