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

University Hospital Tuebingen

Status and phase

Terminated

Phase 2

Conditions

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia

Treatments

Drug: Fludarabine, Thiotepa, Melphalan, Thymoglobuline (ATG)

Study type

Interventional

Funder types

Other

Identifiers

NCT00961142

EudraCT 2007-006016-33

Details and patient eligibility

About

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

Enrollment

23 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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