Dose Finding Study of Thymoglobulin (ATG) in Patients With Steroid-Refractory Acute Graft Versus Host Disease (aGVHD)


Phase 1/Phase 2
N/A
N/A
Not Enrolling
Both
Graft vs Host Disease

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Trial Information

Dose Finding Study of Thymoglobulin (ATG) in Patients With Steroid-Refractory Acute Graft Versus Host Disease (aGVHD)


GvHD is a common side effect of a stem cell transplant. It is caused by a type of white
blood cell (a lymphocyte). ATG is designed to kill lymphocytes and is commonly used to help
prevent or treat GvHD and to treat steroid-refractory aGvHD.

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. You will be
asked questions about your medical history. You will have a complete physical exam. You
will have blood drawn (about 2 tablespoons) for routine tests and to check for any viral
infections. Women who are able to have children must have a negative blood (about 1
teaspoon) or urine pregnancy test. You will also have a biopsy of the site that is suspected
to be affected by aGvHD. The study doctor will describe the type of biopsy procedure you
will have, which will depend on the part of the body that is affected by the disease. If
you had an earlier biopsy performed that confirmed aGvHD, you will not need a biopsy
repeated for this study.

If you are found to be eligible to participate in this study, you will be randomly assigned
(as in the toss of a coin) to 1 of 2 groups. Participants in Group 1 will receive a higher
dose of ATG by vein. Participants in Group 2 will receive a lower dose of ATG by vein. You
will have an equal chance of being in 1 of the 2 groups. Participants in both groups will
receive doses of ATG over 4-6 hours, 1 time a day every other day for a total of 3 doses.

During this study, you will be able to remain on steroids and any other drugs you may be
receiving for treatment of aGvHD (such as tacrolimus or cyclosporine). You will also have
blood drawn (about 1 teaspoon) to learn the effect of ATG on the lymphocytes.

You will be taken off this study, if the disease is stable as determined by the study
doctor, if the disease gets worse, or you experience any intolerable side effects. If you
are taken off this study, your study doctor will discuss other treatment options with you.

After you finish receiving the study medication, you will come to the clinic at regularly
scheduled follow-up visits. At first, you will be seen in the clinic once a week for 1
month. You will also have additional blood drawn (about 2 teaspoons) for biomarker testing
(testing that looks at how the drug is working in your body). After the first month of
follow-up visits, you will come in for visits every other week while you are on this study,
which will continue until you have at least 2 consecutive (back to back) evaluations of the
disease status to see if the disease is stable.

This is an investigational study. ATG is FDA approved and commercially available. You
and/or your insurance provider will be financially responsible for the cost of ATG while you
are on this study. Up to 40 patients will take part in this study. All will be enrolled at
M.D. Anderson.


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Description:

Response assessed at day 56, and a complete response or partial response considered a success. A toxic event defined as a life threatening infection, any death due to infection, or any death considered to be directly related to the administration of ATG.

Outcome Time Frame:

Day 56

Safety Issue:

No

Principal Investigator

Amin M. Alousi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2006-0370

NCT ID:

NCT00409695

Start Date:

December 2006

Completion Date:

August 2007

Related Keywords:

  • Graft Vs Host Disease
  • Acute Graft versus Host Disease
  • aGVHD
  • Blood And Marrow Transplantation
  • Thymoglobulin
  • ATG
  • Graft vs Host Disease

Name

Location
U.T. M.D. Anderson Cancer Center Houston, Texas  77030