Clinical trial NCT00961142: Haploidentical Stem Cell Transplantation With CD3/CD19 Depletion and Reduced Intensity Conditioning in Patients With Acute Leukemia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Keywords: Haploidentical Transplantation
CD3/CD19 Depletion
AML
ALL
Reduced Intensity Conditioning
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2009-08-18
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Evaluation of treatment related mortality after haploidentical HCT
timeFrame: 1 year after HCT
Secondary outcomes:
measure: overall survival
timeFrame: 1, 2 and 5 years after inclusion
measure: Evaluate Engraftment
timeFrame: One year after HCT
measure: Evaluate Toxicity
timeFrame: One year after HCT
measure: Evaluate Disease Free Survival
timeFrame: 1, 2 and 5 years after inclusion
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: University of Dresden Medical Center
city: Essen
country: Germany
facility: Center for Marrow Transplantation, University of Essen
city: Halle
country: Germany
facility: Medical Center University of Halle
city: Hamburg
country: Germany
facility: Medical Center University of Hamburg
city: Muenster
country: Germany
facility: Medical Center University of Muenster
city: Tuebingen
country: Germany
facility: South West German Cancer Center, University of Tuebingen Medical Center
city: Wiesbaden
country: Germany
facility: Deutsche Klinik für Diagnostik
city: Wuerzburg
country: Germany
facility: University of Wuerzburg Medical Center
Study officials:
affiliation: Medical Center University Hospital Tuebingen
name: Wolfgang A. Bethge, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1016/j.exphem.2006.08.009.