Thymoglobulin and Total Lymphoid Irradiation for Hematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00476229
Recruitment Status : Completed
First Posted : May 21, 2007
Results First Posted : August 9, 2011
Last Update Posted : August 7, 2012
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Primary Objective:

1. To determine whether the primary endpoint: the composite success rate, defined as the proportion of patients who are alive at day 100; and are without grade 3-4 Graft versus Host Disease (GVHD); and are without grade 4 toxicity (unrelated to infection); and have engrafted, is likely to be at least 40%.

Secondary Objectives:

  1. To determine the cumulative incidence of chronic graft versus host disease.
  2. To determine the overall and disease free survival.

Condition or disease Intervention/treatment Phase
Lymphoma Leukemia Drug: Thymoglobulin Radiation: Total Lymphoid Irradiation Procedure: Peripheral Blood Stem Cell Infusion Drug: Rituximab Not Applicable

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Detailed Description:

The combination of drugs used for this study will help to weaken your immune system, which may help to allow the donor's blood stem cells to engraft (grow) in your body.

Anti-thymocyte globulin (also called ATG or thymoglobulin) is designed to help reduce the risk of transplant rejection and to help prevent graft versus host disease.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

If you are found to be eligible to take part in this study, you will be admitted to the hospital 12 days before the blood stem cell transplant (BSCT), in order to start the pre-transplant treatments and testing. You will have blood (about 1 tablespoon) drawn for routine tests every day while you are in the hospital (before and after the transplant). After the transplant, this blood will be used to check the status of the transplant and watch for any side effects.

You will receive radiation therapy (total lymphoid irradiation) for a total of 10 days before the planned transplant. Radiation therapy will not be given on the weekends. The last radiation treatment will be on the morning of the day you receive your stem cell transplant.

For a total of 5 days after admission to the hospital, you will also receive ATG. ATG will be given through a catheter (plastic tube) that is placed into the large chest vein. The catheter (called a central venous catheter) will stay in place throughout treatment.

You will receive certain drugs as premedication to try to prevent an allergic reaction to the ATG. These may include drugs like acetaminophen (Tylenol), diphenhydramine (Benadryl), and/or steroids which may include solumedrol or prednisone. Tylenol is given by mouth, and Benadryl and steroids are given either by vein (over 10-15 minutes) or by mouth.

The combination of ATG and radiation will weaken your immune system. A weakened immune system may help to allow your body to "accept" donor cells, and it may decrease the chance of your body rejecting the cells.

If your diagnostic biopsy showed that a certain protein was found on your tumor cells, you may also receive rituximab therapy. If you are eligible for rituximab treatment, you will receive the drug once a week for 4 weeks. You will receive rituximab through the central venous catheter or through a vein over 6-8 hours. The first dose will be given on an outpatient basis at 13 days before the stem cell transplant. The next 3 doses may be given in the hospital or on an outpatient basis. You will receive rituximab 6 days before the transplant, and then 1 and 8 days after the transplant. Tylenol and steroids will be given before the rituximab to try to prevent an allergic reaction.

You will be given tacrolimus to try to prevent graft versus host disease (when the donor's immune cells react against the recipient's body, attacking the recipient's cells and tissues). You will receive tacrolimus either through the central venous catheter (over 24 hours each time) or by mouth starting 3 days before the stem cell transplant. You will continue receiving tacrolimus as long as your doctor feels it is necessary, which could be anywhere from about 3 months to several years. This will depend on factors such as whether or not you have graft versus host disease, how many donor cells are in your blood, and the status of your disease.

Cellcept (MMF) will also be given to try to prevent graft versus host disease, starting 1 day after the transplant and continuing through Days 28-42 after the transplant. The MMF will be given twice a day through the central venous catheter over 2 hours, or by mouth.

After the pre-transplant treatments and testing are finished, you will have the blood stem cell transplant. Blood stem cells from a donor will be infused over about 1 hour through your central venous catheter. This can be done while you are in the hospital or on an outpatient basis at M. D. Anderson. Steroids and Benadryl will be given through the catheter before the stem cell transplant to try to prevent an allergic reaction. The catheter will be removed once you no longer need to be given fluids, blood products, and other treatments through the catheter for graft versus host disease. This may take anywhere from 3 months after the transplant to several years.

You will have additional blood (about 2 tablespoons) drawn, bone marrow aspirations and biopsies, chest CT scans, and/or chest x-rays performed as needed to check the effects of the transplant. You will have transfusions of blood and platelets as needed, and you will have to sign a separate consent document for these transfusions.

Blood (about 1 tablespoon each time) will also be drawn at least 2-3 times a week for at least 100 days after the transplant, or longer if the study doctor feels it is necessary.

Treatment will be given in the hospital or an outpatient basis at M. D. Anderson. You may need to stay in the hospital for 3-4 weeks. You will be taken off the study if your disease gets worse.

This is an investigational study. The FDA has approved the drugs used in this study. Their use together in this study is investigational. Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson Cancer Center.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Total Lymphoid Irradiation, Thymoglobulin, and Rituximab for Allogeneic Transplantation in Lymphoid Malignancies
Study Start Date : June 2006
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2009

Arm Intervention/treatment
Experimental: Radiation + Chemotherapy + BSCT
Total Lymphoid Irradiation (2 times) at 80 cGy daily for five days + Thymoglobulin 1.5 mg/kg intravenous 5 days + Rituximab 375 mg/m^2 intravenous on 4 different days + Blood stem cell transplant (BSCT)
Drug: Thymoglobulin
1.5 mg/kg by vein on Days -11 to -7.
Other Names:
  • Antithymocyte Globulin
  • ATG

Radiation: Total Lymphoid Irradiation
80 cGy daily on days -11 to -7 and -4 to 0.
Other Name: TLI

Procedure: Peripheral Blood Stem Cell Infusion
PBSC infusion administered on day 0.
Other Names:
  • Blood Stem Cell Transplant
  • BSCT

Drug: Rituximab
375 mg/m^2 by vein on days -13, -6, 1, & 8. Only those patients whose tumors express CD20 will receive Rituximab.
Other Name: Rituxan

Primary Outcome Measures :
  1. Composite Success Rate [ Time Frame: Baseline to Day 100, assessment at Day 100 ]
    Defined as the proportions of the patients who are alive at day 100, are without Grade 3-4 Graft Graft-versus-host disease (GVHD), without Grade 4 toxicity (unrelated to infection) and have engrafted. Toxicity grades according to Common Toxicity Criteria (CTC) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age up to 70 years.
  • Patients with lymphoid malignancies (primary refractory or recurrent) beyond first remission or unresponsive to therapy and not eligible for protocols of higher priority. Patients should have had at least a partial remission or have stable disease with prior chemotherapy. Patients with bulky disease (greatest dimension > 5 cm by radiographic or clinical examination are not eligible).
  • Adequate renal function, as defined by serum creatinine <1.8 mg/dL.
  • Adequate hepatic function, as defined by SGPT <3 times upper limit of normal; serum bilirubin and alkaline phosphatase <3 times upper limit of normal.
  • Adequate pulmonary function with Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) >35% of expected corrected for hemoglobin. Exceptions may be allowed for patients with pulmonary involvement after discussing with Principal Investigator.
  • Adequate cardiac function with left ventricular ejection fraction >35%. No uncontrolled arrhythmias or symptomatic cardiac disease.
  • Zubrod performance status <2
  • Patients must have an human leukocyte antigens (HLA) matched, or one A, B, C, DR, or DQ mismatched related or unrelated donor (by high resolution typing). Donor must be willing to donate peripheral blood progenitor cells.
  • Patient should be willing to participate in the study by providing written consent.
  • Negative beta human chorionic gonadotrophin (hCG) test in a woman of child bearing potential (defined as not post menopausal for 12 months or no previous surgical sterilization).

Exclusion Criteria:

  • Patients with active central nervous system (CNS) disease.
  • Evidence of acute or chronic active hepatitis or cirrhosis.
  • Uncontrolled infection, including Hepatitis B, C, Human immunodeficiency virus (HIV) or human T-cell lymphotropic virus type 1 (HTLV-1) infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00476229

United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genzyme, a Sanofi Company
Principal Investigator: Chitra M. Hosing, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00476229     History of Changes
Other Study ID Numbers: 2005-0892
First Posted: May 21, 2007    Key Record Dates
Results First Posted: August 9, 2011
Last Update Posted: August 7, 2012
Last Verified: August 2012

Keywords provided by M.D. Anderson Cancer Center:
Non-Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Hodgkin's Lymphoma
Mycophenolate Mofetil
Total Lymphoid Irradiation

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Immunosuppressive Agents