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

Phase 2

Terminated

• Conditions: Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia

• Registration Number: NCT00961142
• Lead Sponsor: University Hospital Tuebingen

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

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-08-17
• Study First Submitted QC: 2009-08-17
• Study First Posted: 2009-08-18
• Primary Completion: 2015-12-30
• Study Completion: 2015-12-30
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-29
• Last Update Posted: 2022-07-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 23

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Evaluation of treatment related mortality after haploidentical HCT	1 year after HCT	Cumulative Incidence of treatment related mortality

Secondary Outcome Measures

Name	Time	Method
Evaluate Engraftment	One year after HCT
Evaluate Toxicity	One year after HCT
Evaluate Disease Free Survival	1, 2 and 5 years after inclusion
overall survival	1, 2 and 5 years after inclusion	by Kaplan-Meier

Trial Locations

Locations (8)

South West German Cancer Center, University of Tuebingen Medical Center; 🇩🇪 Tuebingen, Germany

Medical Center University of Hamburg; 🇩🇪 Hamburg, Germany

Deutsche Klinik für Diagnostik; 🇩🇪 Wiesbaden, Germany

University of Dresden Medical Center; 🇩🇪 Dresden, Germany

Center for Marrow Transplantation, University of Essen; 🇩🇪 Essen, Germany

Medical Center University of Muenster; 🇩🇪 Muenster, Germany

Medical Center University of Halle; 🇩🇪 Halle, Germany

University of Wuerzburg Medical Center; 🇩🇪 Wuerzburg, Germany