Thymoglobuline in Non-myeloablative Allogeneic Stem-cell Transplantation

NCT00130754 | Completed Phase 3

• 1 other identifier: 39-14.01.05-HMO-CTIL
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic stem cell transplantation is the treatment of choice for a growing number of malignant and non-malignant indications. Until recently, myeloablative in conjunction with immunosuppressive conditioning was considered mandatory for the elimination of malignant hematopoietic cells and to prevent graft rejection. The aim of allogeneic non-myeloablative stem cell transplantation (NST) is to induce host-to-graft tolerance with fast and durable engraftment of donor stem cells, by means of conditioning, which is well-tolerated by patients. The rationale behind the NST strategy is to induce optimal graft-versus-leukemia (GVL) effects for the elimination of all malignant cells by alloreactive immunocompetent cells from a matched donor as an alternative to standard high-dose myeloablative chemo radiotherapy. The NST protocol is therefore mainly based on immunosuppression and thus contains fludarabine, low dose busulfan and anti-T-lymphocyte globulin (ATG). Thymoglobuline is a polyclonal rabbit antiserum specific for human T cells used in organ transplantation for induction of tolerance and rejection prevention and treatment. It was also used in stem-cell transplantation (SCT) for the same purposes (e.g. for generation of tolerance and rejection preclusion) as well as a treatment for graft-versus-host disease (GVHD). Data from myeloablative protocols suggest that ATG before SCT significantly reduces the risk for grade III-IV acute GVHD. This does not translate to a reduction in transplant-related mortality (TRM) because of the increased risk for infections and thus survival is unchanged. Extensive chronic GVHD was also significantly shown to be reduced in patients receiving ATG in the myeloablative setting. However, the role of ATG in the NST protocol was never evaluated in a prospective randomized trial. In view of the preliminary data suggesting of an additive effect of ATG in these circumstances we, the investigators at Hadassah Medical Organization, evaluate the effect of ATG in NST by a prospective randomized trial.

Conditions

Stem Cell Transplantation; Graft Vs Host Disease

Outcome Measures

Primary Outcomes (2)

• Acute GVHD occurrence

  100d

• Acute GVHD grading

  100d

Secondary Outcomes (9)

• Time to acute GVHD

  100d

• Chronic GVHD occurrence

  1y

• Chronic GVHD grading

  1y

• Engraftment/graft rejection

  21d

• Overall survival

  1y

Study Arms (2)

1

EXPERIMENTAL

Thymo

Drug: Thymoglobuline

2

NO INTERVENTION

Interventions

Thymoglobuline DRUG

IV 7.5 mg/kg

1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ages 18-75 years old with a disease necessitating allogeneic SCT.
• Patients must have an HLA compatible donor willing and capable of donating peripheral blood stem cells preferably, or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated (HLA compatible defined as 5/6 or 6/6 matched related \[A, B, DR\] or 8/8 molecular \[A, B, C, DR\] matched unrelated donor).
• Both patients and donor must sign written informed consents.
• Patients must have an ECOG performance status (PS) ≤ 2; Creatinine \< 2.0 mg/dl; Ejection fraction \> 40%; Diffusing capacity of the lung for carbon monoxide (DLCO) \> 50% of predicted; Serum bilirubin \< 3 gm/dl; Elevated GPT or GOT \> 3 x normal values.

You may not qualify if:

• Active life-threatening infection
• Overt untreated infection
• Hypersensitivity to thymoglobuline or other rabbit produced immunoglobulin.
• HIV seropositivity, hepatitis B or C antigen positivity with active hepatitis
• Pregnant or lactating women.
• Donor contraindication (HIV seropositive confirmed by Western Blot; hepatitis B antigenemia; evidence of bone marrow disease; unable to donate bone marrow or peripheral blood due to concurrent medical condition).
• Inability to comply with study requirements.

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Medical Organization

Jerusalem, 91120, Israel

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Michael Y Shapira, MD

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 15, 2005
• First Posted: August 16, 2005
• Study Start: February 1, 2005
• Study Completion: November 1, 2007
• Last Updated: February 23, 2011

Record last verified: 2007-11

Locations

IL (1)