Thymoglobulin and Total Lymphoid Irradiation for Hematologic Malignancies

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00476229
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 35
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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	N/A

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 Design

• Study Type: Interventional
• 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: Jun 1, 2006
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

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 Names: 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 Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Composite Success Rate [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 70 Years
• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	U.T.M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Chitra M. Hosing, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00476229
• Other Study ID Numbers: 2005-0892
• First Posted: May 21, 2007
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Hodgkin's Lymphoma; Lymphoma; Leukemia; Mycophenolate Mofetil; Tacrolimus; Thymoglobulin; Total Lymphoid Irradiation
• Additional relevant MeSH terms: Lymphoma; Leukemia; Rituximab; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Recruitment Details	Recruitment period: July 14, 2006 to October 15, 2008. All patients were registered at UT MD Anderson Cancer Center.

Arm/Group Title	Radiation + Chemotherapy + BSCT
Arm/Group Description	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)
Period Title: Overall Study
STARTED	20
COMPLETED	19
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Radiation + Chemotherapy + BSCT
Arm/Group Description	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)
Overall Participants	20
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	30
Sex: Female, Male (Count of Participants)
Female	10 50%
Male	10 50%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Composite Success Rate
Description	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.
Time Frame	Baseline to Day 100, assessment at Day 100

Outcome Measure Data

Analysis Population Description

Analysis was per protocol. One participant was inevaluable.

Arm/Group Title	Radiation + Chemotherapy + BSCT
Arm/Group Description	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)
Measure Participants	19
Engraftment	100 500%
Acute GvHD	75 375%
alive at 100 days	84 420%

Adverse Events

Time Frame	2 year, 5 months
Arm/Group Title	Radiation + Chemotherapy + BSCT
Arm/Group Description	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)
All Cause Mortality
	Radiation + Chemotherapy + BSCT
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Radiation + Chemotherapy + BSCT
	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)
Hepatobiliary disorders
increased bilrubin	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	Radiation + Chemotherapy + BSCT
	Affected / at Risk (%)	# Events
Total	19/19 (100%)
Cardiac disorders
low blood pressure	7/19 (36.8%)	7
dysrhythmias	1/19 (5.3%)	1
tachycardia	4/19 (21.1%)	4
edema	5/19 (26.3%)	5
arterial	2/19 (10.5%)	2
other cardiac	5/19 (26.3%)	5
pain	2/19 (10.5%)	2
pericardial	1/19 (5.3%)	1
Endocrine disorders
other endocrine	3/19 (15.8%)	3
Eye disorders
eye pain	2/19 (10.5%)	2
Gastrointestinal disorders
diarrhea	1/19 (5.3%)	1
nausea	9/19 (47.4%)	9
Gastrointestinal other	13/19 (68.4%)	13
diarrhea	5/19 (26.3%)	5
Anorexia	1/19 (5.3%)	1
bleeding	2/19 (10.5%)	2
vomiting	2/19 (10.5%)	2
pain	3/19 (15.8%)	3
General disorders
fatigue	7/19 (36.8%)	7
rigors	2/19 (10.5%)	2
other general disorders	7/19 (36.8%)	7
fever	7/19 (36.8%)	7
Hepatobiliary disorders
increased Alkaline phosphatase	7/19 (36.8%)	7
increased ALT	9/19 (47.4%)	9
increased biblrubin	5/19 (26.3%)	5
increased LDH	3/19 (15.8%)	3
Infections and infestations
infection	1/19 (5.3%)	1
Metabolism and nutrition disorders
hypercalcemia	2/19 (10.5%)	2
hyperglycemia	8/19 (42.1%)	8
hypermagesium	4/19 (21.1%)	4
hypocalcemia	1/19 (5.3%)	1
hypokalemia	1/19 (5.3%)	1
metabolic other	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
motor	3/19 (15.8%)	3
other neruologic	6/19 (31.6%)	6
Nervous system disorders
headache	9/19 (47.4%)	9
insomnia	2/19 (10.5%)	2
neurologic mood	4/19 (21.1%)	4
Renal and urinary disorders
increased creatinine	5/19 (26.3%)	5
cystitis	3/19 (15.8%)	3
Respiratory, thoracic and mediastinal disorders
pneumonitis	2/19 (10.5%)	2
cough	5/19 (26.3%)	5
shortness of breath	5/19 (26.3%)	5
Skin and subcutaneous tissue disorders
rash	7/19 (36.8%)	7
skin other	3/19 (15.8%)	3
alopecia	1/19 (5.3%)	1

Limitations/Caveats

Early termination due to financial support.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.