Total Lymphoid Irradiation and Anti-Thymocyte Globulin in the Allogeneic Hematopoietic Cell Transplantation (TLI)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Fondazione Neoplasie Sangue Onlus.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Fondazione Neoplasie Sangue Onlus
ClinicalTrials.gov Identifier:
NCT01081405
First received: March 2, 2010
Last updated: March 4, 2010
Last verified: March 2010
  Purpose

To exploit the curative potential of allografting, the ultimate clinical goal is to separate GVL from GVHD. In murine preclinical models, recipients of allogeneic hematopoietic cell transplants after a preparative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) did not develop GVHD. The murine TLI/ATG study was turned into a clinical phase I protocol for patients with hematological malignancies, and a reduction of acute GVHD to < 3% was observed (Lowsky R et al, N Engl J Med). This suggests that specific immune mechanisms control GVHD and preserve GVL. The study will include patients with lympho and myeloproliferative diseases. The conditioning regimen will consist of TLI [ten 80 cGy fractions on day -11 through day -7 and on day -4 through day -1; the radiation field (four fields—two anterior and two posterior) involves all major lymphoid organs including the thymus, spleen and lymph nodes] and ATG (five i.v. doses at 1.5 mg/kg/day from day -11 through day -7). G-CSF mobilised hematopoietic cells, collected on days -1 and 0, from HLA-identical siblings or unrelated donors will be infused on day 0. Post-transplant immunosuppression will consist of oral cyclosporine (at 6.25 mg/kg/d) from day -3 and micophenolate mophetile (at 15 mg/Kg bid) from day +1. The clinical primary objective is to reduce the incidence of GVHD to < 5%, with better survival and quality of life.


Condition Intervention Phase
Hematologic Malignancies
Other: TOTAL LYMPHOID IRRADIATION
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Fondazione Neoplasie Sangue Onlus:

Primary Outcome Measures:
  • Primary Outcome Measure not applicable [ Time Frame: Not reached ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2007
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: TOTAL LYMPHOID IRRADIATION
    Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients with Hematologic Malignancies
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   50 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

(A) Any patient with one of the following hematolymphoid malignancies or syndromes in whom allogeneic NST is warranted. Specific disease categories include: indolent advanced stage Non-Hodgkin Lymphomas, Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, Hodgkin Disease, Acute Leukemias in any complete remission, Aplastic Anemia, Paroxsymal Nocturnal Hemoglobinuria, Myelodysplastic and Chronic Myeloproliferative Syndromes, Multiple Myeloma. Patients with other selected malignancies/disorders may also be considered but must be approved by the transplant team and the Principal Investigator.

(B) Elderly patients age > 50 < 70 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, or because of refusal to undergo conventional myeloablative regimes.

(C) A fully HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.

(D) Patient must be competent to give consent.

Exclusion Criteria:

(A) Patients with progressive hematolymphoid malignancies despite conventional therapies, or acute leukemias not in complete remission.

(B) Uncontrolled CNS involvement with disease

(C) Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment

(D) Females who are pregnant

(E) Organ dysfunction defined as follows:

  • Cardiac function: ejection fraction <30% or uncontrolled cardiac failure
  • Pulmonary: DLCO <40% predicted
  • Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or transaminases >4x the upper limit of normal
  • Renal: creatinine clearance <50 cc/min (24 hour urine collection)

(F) Karnofsky performance score < 60%

(G) Patients with poorly controlled hypertension on multiple antihypertensives

(H) Documented fungal disease that is progressive despite treatment

(I) Viral infections: HIV positive patients. Hepatitis B and C positive patients will be evaluated on a case by case basis

(J) 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.

  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: NCT01081405

Contacts
Contact: Mario Boccadoro, MD +39 0116335814 gismm2001@yahoo.com
Contact: Benedetto Bruno, MD +39 0116334354 benedetto.bruno@unito.it

Locations
Italy
A.O.U. San Giovanni Battista Recruiting
Torino, Italy, 10126
Contact: Mario Boccadoro, MD    +39 0116335814    gismm2001@yahoo.it   
Contact: Benedetto Bruno, MD    +39 0116334354    benedetto.bruno@unito.it   
Principal Investigator: Mario Boccadoro, MD         
Sponsors and Collaborators
Fondazione Neoplasie Sangue Onlus
Investigators
Principal Investigator: Mario Boccadoro, MD Division of Hematology - University of Torino - A.O.U. San Giovanni Battista
  More Information

No publications provided

Responsible Party: Dr. Mario Boccadoro, Fondazione Neoplasie Sangue Onlus
ClinicalTrials.gov Identifier: NCT01081405     History of Changes
Other Study ID Numbers: TLI-001-2007, 2007−005563−10
Study First Received: March 2, 2010
Last Updated: March 4, 2010
Health Authority: Italy: Ministry of Health

Keywords provided by Fondazione Neoplasie Sangue Onlus:
ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION
TOTAL LYMPHOID IRRADIATION
ANTI-THYMOCYTE GLOBULIN

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014