Thymoglobulin (ATG) Dose Finding Study

• Status: Terminated
• Trial end date: 2007-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective:

• To determine the response and toxicity rate at day 56 of two different dose levels of thymoglobulin (ATG) [anti-thymocyte globulin (rabbit)] as a treatment of steroid-refractory acute graft versus host disease (aGVHD).

Secondary Objectives:

• To evaluate the response rate at day 28.

• To evaluate the overall survival and non-relapse mortality at 6 months.

• To determine the toxicity profile of thymoglobulin when used for the treatment of steroid-refractory aGVHD in each of two dose schedules.

• To characterize the pharmacokinetic profile of thymoglobulin in each of two dose schedules.

• To analyze biomarkers of cellular drug effect by quantifying T-cell apoptosis in aims of finding the minimal effective dose.

• To determine immune-reconstitution after administration of thymoglobulin to patients with steroid-refractory aGVHD for each dose schedule.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Genzyme, a Sanofi Company
• Treatments: Antilymphocyte Serum; Thymoglobulin

Criteria

Inclusion Criteria:

1. Patients who underwent their first allogeneic transplant for any malignancy and with any cell (bone marrow, peripheral stem cell, cord blood) or donor (matched or mismatched related or unrelated) source.

2. Biopsy-proven, grade II-IV aGVHD following allogeneic hematopoietic stem cell transplantation (HSCT) of any source (bone marrow, peripheral blood or cord blood stem cells). Enrollment may be started prior to results of biopsy in cases of high clinical suspicion for aGVHD.

3. Early steroid-refractory aGVHD. This is defined as any NR or PD after a minimum of 3 days and not more than 1 week of 1 mg/kg/day of methylprednisolone.

4. Ability to sign informed consent.

5. Ability to return for clinical follow-up as specified in the protocol.

6. Inability to taper as defined by patients on < or = 1 mg/kg/day of methylprednisolone but unable to further taper without resultant increase of acute GVHD stage.

7. Patients with a reflare of a GVHD defined as worsening of 1 stage of acute GVHD in a patient who initially responded.

Exclusion Criteria:

1. Relapsed malignancy.

2. Acute GVHD as a result of a second or subsequent transplant or donor lymphocyte infusion (DLI).

3. Active, uncontrolled infection.

4. Patients who have received any second-line of immunosuppressive treatment for GVHD beyond corticosteroids and calcineurin inhibitors. Topical steroids, oral budesonide and extracorporeal photochemotherapy started at the time of steroids are allowed.

5. Life-threatening infusion reaction or hypersensitivity to any formulation of ATG in the past.

6. Patients who are pregnant or are breast feeding.