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

Acute Myeloid Leukemia Clinical Trial

— CD3/CD19 Haplo  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00961142
• Other study ID #: EudraCT 2007-006016-33
• Status: Terminated
• Phase: Phase 2
• Start date: June 2009
• Est. completion date: December 30, 2015

Study information

• Verified date: June 2022
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: December 30, 2015
• Est. primary completion date: December 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
Germany	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	Muenster
Germany	South West German Cancer Center, University of Tuebingen Medical Center	Tuebingen
Germany	Deutsche Klinik für Diagnostik	Wiesbaden
Germany	University of Wuerzburg Medical Center	Wuerzburg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Bethge WA, Faul C, Bornhäuser M, Stuhler G, Beelen DW, Lang P, Stelljes M, Vogel W, Hägele 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. Epub 2007 Sep 14. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of treatment related mortality after haploidentical HCT	Cumulative Incidence of treatment related mortality	1 year after HCT
Secondary	overall survival	by Kaplan-Meier	1, 2 and 5 years after inclusion
Secondary	Evaluate Engraftment		One year after HCT
Secondary	Evaluate Toxicity		One year after HCT
Secondary	Evaluate Disease Free Survival		1, 2 and 5 years after inclusion

External Links

•   Homepage BMT-Study Group Tuebingen