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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Nantes University Hospital
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT01566656
First received: March 27, 2012
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

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

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

  • 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.

  • 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.


Estimated Enrollment: 30
Study Start Date: March 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   50 Years to 66 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566656

Contacts
Contact: Mohamad MOHTY, Pr 01 49 28 26 20 mohamad.mohty@inserm.fr

Locations
France
Besançon University Hospital Recruiting
Besançon, France
Contact: Eric DECONINCK, Pr    03 81 66 82 32    edeconinck@chu-besancon.fr   
Principal Investigator: Eric DECONINCK, Pr         
Bordeaux University Hospital Not yet recruiting
Bordeaux, France
Contact: Noël MILPIED, Pr    05 57 65 60 53    noel.milpied@chu-bordeaux.fr   
Principal Investigator: Noël MILPIED, Pr         
Caen University Hospital Recruiting
Caen, France
Contact: REMAN, Dr    02 31 27 26 39    reman-o@chu-caen.fr   
Principal Investigator: REMAN, Dr         
Clermont-Ferrand University Hospital Recruiting
Clermont-Ferrand, France
Contact: Jacques-Olivier BAY, Pr    04 73 75 00 65    jobay@chu-clermontferrand.fr   
Principal Investigator: Jacques-Olivier BAY, Pr         
Lille University Hospital Recruiting
Lille, France
Contact: Ibrahim YACOUB-AGHA, Pr    03 20 44 55 51    i-yakoub-agha@chru-lille.fr   
Principal Investigator: Ibrahim YACOUB-AGHA, Pr         
Lyon University Hospital Recruiting
Lyon, France
Contact: Mauricette MICHALLET, Pr    04 72 11 74 02    mauricette.michallet@chu-lyon.fr   
Principal Investigator: Mauricette MICHALLET, Pr         
Nantes University Hospital Recruiting
Nantes, France
Contact: Patrice CHEVALLIER, Dr       patrice.chevallier@chu-nantes.fr   
Principal Investigator: Patrice CHEVALLIER, Dr         
Hôpital Saint Antoine Recruiting
Paris, France, 75571
Contact: RUBIO Marie-Thérèse, Dr    01 49 28 26 20      
Principal Investigator: Marie-Thérèse RUBIO, Dr         
Sponsors and Collaborators
Nantes University Hospital
Investigators
Principal Investigator: Mohamad MOHTY, Pr Hôpital Saint Antoine (AP-HP)
  More Information

No publications provided

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT01566656     History of Changes
Other Study ID Numbers: 10/6-L
Study First Received: March 27, 2012
Last Updated: October 23, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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:
Neoplasms
Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 28, 2014