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

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

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

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Fludarabine, Thiotepa, Melphalan, Thymoglobuline (ATG)

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, D-01307
    • University of Dresden Medical Center
  • Essen, Germany, 45122
    • Center for Marrow Transplantation, University of Essen
  • Halle, Germany, 06120
    • Medical Center University of Halle
  • Hamburg, Germany, 20246
    • Medical Center University of Hamburg
  • Muenster, Germany, 48149
    • Medical Center University of Muenster
  • Tuebingen, Germany, 72076
    • South West German Cancer Center, University of Tuebingen Medical Center
  • Wiesbaden, Germany, 65191
    • Deutsche Klinik für Diagnostik
  • Wuerzburg, Germany, D-97070
    • University of Wuerzburg Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of treatment related mortality after haploidentical HCT	Cumulative Incidence of treatment related mortality	1 year after HCT

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Wolfgang A. Bethge, MD, Medical Center University Hospital Tuebingen

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Homepage BMT-Study Group Tuebingen

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): December 30, 2015
• Study Completion (Actual): December 30, 2015

Study Registration Dates

• First Submitted: August 17, 2009
• First Submitted That Met QC Criteria: August 17, 2009
• First Posted (Estimate): August 18, 2009

Study Record Updates

• Last Update Posted (Actual): July 5, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: AML; ALL; Haploidentical Transplantation; Reduced Intensity Conditioning; CD3/CD19 Depletion
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Fludarabine; Thiotepa; Thymoglobulin
• Other Study ID Numbers: EudraCT 2007-006016-33

Plan for Individual participant data (IPD)

Study Data/Documents

1. Results