Thymoglobuline in Non-myeloablative Allogeneic Stem-cell Transplantation

• Sponsor: Hadassah Medical Organization
• Information provided by: Hadassah Medical Organization

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Stem Cell Transplantation; Graft Vs Host Disease	Drug: Thymoglobuline	Phase 3

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	30 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	A Prospective Randomized, Controlled Pilot Study in Order to Evaluate the Place of Thymoglobuline in Non-myeloablative Allogeneic Hemapoietic Stem-cell Transplantation (NST)
Study Start Date :	February 2005
Actual Study Completion Date :	November 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Thymo	Drug: Thymoglobuline; IV 7.5 mg/kg
No Intervention: 2

Outcome Measures

Primary Outcome Measures :

1. Acute GVHD occurrence [ Time Frame: 100d ]
2. Acute GVHD grading [ Time Frame: 100d ]

Secondary Outcome Measures :

1. Time to acute GVHD [ Time Frame: 100d ]
2. Chronic GVHD occurrence [ Time Frame: 1y ]
3. Chronic GVHD grading [ Time Frame: 1y ]
4. Engraftment/graft rejection [ Time Frame: 21d ]
5. Overall survival [ Time Frame: 1y ]
6. Disease free survival [ Time Frame: 1y ]
7. Infections [ Time Frame: 1y ]
8. Transplant-related mortality (TRM) [ Time Frame: 1y ]
9. Transplant-related toxicity (TRT) [ Time Frame: 1y ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Not fulfilling any of the inclusion criteria
• 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.

Contacts and Locations

Locations

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Israel
Hadassah Medical Organization
Jerusalem, Israel, 91120

Sponsors and Collaborators

Hadassah Medical Organization

Investigators

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Principal Investigator:	Michael Y Shapira, MD	Hadassah Medical Organization

More Information

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ClinicalTrials.gov Identifier:	NCT00130754 History of Changes
Other Study ID Numbers:	39-14.01.05-HMO-CTIL
First Posted:	August 16, 2005
Last Update Posted:	February 23, 2011
Last Verified:	November 2007

Additional relevant MeSH terms:

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Graft vs Host Disease; Immune System Diseases; Thymoglobulin; Antilymphocyte Serum	Immunologic Factors; Physiological Effects of Drugs; Immunosuppressive Agents