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

NCT01081405 | Completed DMC

• 2 other identifiers: TLI-001-20072007-005563-10
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HEMATOLOGIC MALIGNANCIES

Keywords

ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION; TOTAL LYMPHOID IRRADIATION; ANTI-THYMOCYTE GLOBULIN

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure not applicable

  Not reached

Study Arms (1)

TOTAL LYMPHOID IRRADIATION

EXPERIMENTAL

Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients with Hematologic Malignancies

Other: TOTAL LYMPHOID IRRADIATION

Interventions

TOTAL LYMPHOID IRRADIATION OTHER

Allogeneic Hematopoietic Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Patients with Hematologic Malignancies

TOTAL LYMPHOID IRRADIATION

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• (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.

Sponsors & Collaborators

• Fondazione EMN Italy Onlus: lead

Study Sites (1)

A.O.U. Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2010
• First Posted: March 5, 2010
• Study Start: November 1, 2007
• Primary Completion: November 1, 2022
• Study Completion: November 1, 2022
• Last Updated: March 13, 2024

Record last verified: 2024-03

Locations

IT (1)