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Allogeneic Hematopoietic Stem Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-thymocyte Globulin for Older Patients With Relapsed Lymphoid Malignancies (TLI-ATG)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01566656
Recruitment Status : Completed
First Posted : March 29, 2012
Last Update Posted : April 5, 2018
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:
Recent advances in allogeneic hematopoietic cell transplantation (allo-SCT) have led to reduce intensity preparative regimens that are non-myeloablative and reduce the toxicities associated with the transplant. Consequently non-relapse mortality has been reduced, including in elderly patients with comorbidities. However, despite this benefit in terms of toxicity, excessive reduction of the intensity preparative regimens may favor relapse of the initial illness. Thus, acute and chronic graft-versus-host disease and opportunistic fungal and viral infections are always serious complications. The aim of our study is to check if a new modality of reduced intensity preparative regimen combining total lymphoid irradiation (TLI) and thymoglobulin (ATG), would limit the toxicity of treatment and reduce the incidence of acute GVHD after allogeneic transplantation while preserving the antitumor benefit.

Condition or disease Intervention/treatment Phase
Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is Warranted Drug: total lymphoid irradiation and anti-thymocyte globulin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-thymocyte Globulin for Older Patients With Relapsed Lymphoid Malignancies
Actual Study Start Date : March 2, 2012
Actual Primary Completion Date : November 29, 2016
Actual Study Completion Date : November 29, 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: TLI and anti-thymocyte globulin Drug: total lymphoid irradiation and anti-thymocyte globulin
  • TLI Administration: TLI is administered ten times in 120 cGy fractions on day -11 through day -7 and day -4 through day -1.
  • ATG: Thymoglobulin will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg.
  • Mobilized PBSCs (Day 0): The desired cell doses (based on recipient body weight) for MRD and MUD transplants are around 4-8 x106 CD34+ cells/kg.
  • GVHD Prophylaxis: Cyclosporine A (CSP) 3 mg/kg IV from day-3 and Mycophenylate mofetil (MMF) 500 mg x 4/ day PO from day 0

Primary Outcome Measures :
  1. To evaluate the incidence of non-relapse mortality (NRM) [ Time Frame: one year after transplantation ]

Secondary Outcome Measures :
  1. Neutrophil and platelets recovery and chimerism measurement
    To evaluate the kinetics of donor hematopoietic cell engraftment (neutrophil and platelets recovery) and chimerism.

  2. T cell subsets, regulatory cells, NK cells and B cells measurement
    To document the quantitative and qualitative reconstitution of the immune system including T cell subsets, regulatory cells, NK cells and B cells.

  3. Number of relapse, acute and chronic GVHD [ Time Frame: one year after transplantation ]
    To evaluate the rate of relapse, overall and event-free survival and incidence of acute and chronic GVHD, at one year after transplantation.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 66 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Any patient with one of the following hemato-lymphoid malignancies or syndromes in whom allogeneic stem cell transplantation is warranted. Specific disease categories include: non-follicular indolent advanced stage Non-Hodgkin Lymphomas, Mantle Cell Lymphoma, Marginal zone lymphoma, MALT, T cell lymphoma, Chronic Lymphocytic or prolymphocytic Leukemia, Hodgkin Disease, and Waldenström macroglobulinemia. T-cell NOS, angioimmunoblastic lymphoma, HTLV1, T-gamma/delta, anaplastic lymphoma and Sezeay syndromes can be included after careful assessment by the PI and the protocol steering committee.
  • Patients must be at least in partial remission (according to standard criteria) after salvage therapy and before (~one month) the start of the conditioning regimen.
  • Patient age >50 and less than 66 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants.
  • A fully HLA-identical sibling or matched unrelated donor is available (10/10 HLA match). Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
  • Patient must be competent to give consent.

Exclusion Criteria:

  • Patients with progressive hematolymphoid malignancies despite conventional therapies, and not in partial remission during the month preceding transplantation.
  • Patients with DLBCL or cutaneous T cell lymphoma
  • Uncontrolled CNS involvement with disease
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant
  • Organ dysfunction defined as follows:
  • Cardiac function: ejection fraction <30% or uncontrolled cardiac failure
  • Pulmonary: DLCO <40% predicted
  • Renal: Serum creatinine >1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m²
  • Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or transaminases >4x the upper limit of normal
  • Karnofsky performance score < 70%
  • Patients with poorly controlled hypertension on multiple antihypertensives
  • Documented fungal disease that is progressive despite treatment
  • Viral infections: HIV positive patients. Hepatitis B and C positive patients will be evaluated on a case by case basis
  • Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.
  • Patients with prior malignancies diagnosed > 5 years ago without evidence of disease are eligible. Patients with a prior malignancy treated < 5 years ago but have a life expectancy of > 5 years for that malignancy are eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01566656

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Besançon University Hospital
Besançon, France
Lille University Hospital
Lille, France
Lyon University Hospital
Lyon, France
Nantes University Hospital
Nantes, France
Sponsors and Collaborators
Nantes University Hospital
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Principal Investigator: Mohamad MOHTY, Pr Hôpital Saint Antoine (AP-HP)

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Responsible Party: Nantes University Hospital Identifier: NCT01566656     History of Changes
Other Study ID Numbers: BRD/10/06-L
First Posted: March 29, 2012    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: April 2018

Keywords provided by Nantes University Hospital:
Allogeneic hematopoietic stem cell transplantation
Non-myeloablative preparative regimen
Total lymphoid irradiation
Anti-thymocyte globulin
Lymphoid malignancies

Additional relevant MeSH terms:
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Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents