Rituximab (Rituxan) for the Prevention of EBV-LPD Epstein Barr Virus (EBV) Lymphoproliferative Disorder Post T Cell Depleted Unrelated and HLA Mis-matched Related HSCT

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00648037
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arm: 1
• Duration (Months): 9
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if we can prevent Epstein Barr Virus lymphomas by the monthly administration of an (antibody) protein against B lymphocytes called Rituximab. Although this medicine has been approved by the Food and Drug Administration to treat patients with other types of lymphomas, and has been used to treat a small number of patients with EBV lymphomas and other types of B-cell leukemias, it has not been approved to try and prevent EBV-lymphomas. Use of Rituximab to try to prevent EBV-lymphomas is therefore experimental.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin's Disease; Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma	Drug: Rituximab	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Trial of Rituximab (Rituxan) for the Prevention of EBV-LPD Post T Cell Depleted Unrelated and HLA Mis-matched Related HSCT
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rituximab Patients following a T cell depleted HLA-mis-matched related or unrelated hematopoietic stem cell transplant (HSCT) will be treated with monthly Rituximab.	Drug: Rituximab; Rituximab 375 mg/m^2 starting approximately 1 month post transplant (no later than day 45), and continuing monthly until the CD4 cell count is > 200 cells/ul or a maximum of 6 doses have been given.

Outcome Measures

Primary Outcome Measures

1. Safety of Rituximab Prophylaxis [3 months post transplant]

   The following stopping rules will be employed to determine that the risks of graft failure, severe GvHD, treatment-related mortality, infection, and EBV-LPD in study patients are not increased over expected. In addition, patients will be removed from study if they develop irreversible non-hematologic Grade III toxicity or any Grade IV toxicity felt to be related or possibly related to study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient must be a recipient of aT cell depleted unrelated or HLA mis-matched related HSCT for the treatment of a malignancy or immunodeficiency disease.

• Patients must have an ANC > or = to 1500 cells/ul on the day of first treatment.

• Patients with acute or chronic leukemia, or MDS prior to transplant must be in remission defined as <5% blasts in the bone marrow.

• Patient with must be in remission.

• Patient must be Hepatitis B surface antigen negative pre transplant.

• Patients must have adequate cardiac function defined as a left ventricular ejection fraction at rest of >50% documented pre-transplant.

• Patient may be of either gender and of any ethnic background.

• Patient may be of any age. There is no upper age restriction.

• Patients or their guardians must be able to understand the nature and risk of the proposed study and be able to sign consent.

Exclusion Criteria:

• Karnofsky score <70%

• Female patients who are pregnant or lactating.

• Evidence of EBV-LPD or circulating EBV copy number >1000.

• Active uncontrolled bacterial or fungal infection.

• Prior history of Hepatitis B infection or Hepatitis B surface antigen positivity pre transplant.

• HIV-1,2 sero-positive patients.

• Patients or guardians not signing informed consent.

• Patients with prior allergic reaction to Rituximab or other murine monoclonal antibody.

• Patients taking other investigational agents under another protocol unless discussed and approved in advance by Genentech and the IDEC Therapeutic Director.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Trudy Small, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00648037
• Other Study ID Numbers: 01-118
• First Posted: Apr 1, 2008
• Last Update Posted: Feb 1, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: RITUXIMAB; Lymphoma
• Additional relevant MeSH terms: Hodgkin Disease; Myelodysplastic Syndromes; Rituximab

Study Results

Participant Flow

Arm/Group Title	Rituximab Prophylaxis in TCD Unrelated or HLA Mismatched HSCT
Arm/Group Description	To determine the safety of Rituximab prophylaxis in patients following TCD unrelated or HLA mismatched related HSCT
Period Title: Overall Study
STARTED	26
COMPLETED	10
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Rituximab Prophylaxis in TCD Unrelated or HLA Mismatched HSCT
Arm/Group Description	To determine the safety of Rituximab prophylaxis in patients following TCD unrelated or HLA mismatched related HSCT
Overall Participants	26
Age (Count of Participants)
<=18 years	9 34.6%
Between 18 and 65 years	16 61.5%
>=65 years	1 3.8%
Sex: Female, Male (Count of Participants)
Female	9 34.6%
Male	17 65.4%

Outcome Measures

1. Primary Outcome

Title	Safety of Rituximab Prophylaxis
Description	The following stopping rules will be employed to determine that the risks of graft failure, severe GvHD, treatment-related mortality, infection, and EBV-LPD in study patients are not increased over expected. In addition, patients will be removed from study if they develop irreversible non-hematologic Grade III toxicity or any Grade IV toxicity felt to be related or possibly related to study drug.
Time Frame	3 months post transplant

Outcome Measure Data

Analysis Population Description

Please see Adverse Event section for more details.

Arm/Group Title	Rituximab Prophylaxis in TCD Unrelated or HLA Mismatched HSCT
Arm/Group Description	To determine the safety of Rituximab prophylaxis in patients following TCD unrelated or HLA mismatched related HSCT
Measure Participants	26
Number [participants]	23 88.5%

Adverse Events

Arm/Group Title	Rituximab Prophylaxis in TCD Unrelated or HLA Mismatched HSCT
Arm/Group Description	To determine the safety of Rituximab prophylaxis in patients following TCD unrelated or HLA mismatched related HSCT
All Cause Mortality
	Rituximab Prophylaxis in TCD Unrelated or HLA Mismatched HSCT
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rituximab Prophylaxis in TCD Unrelated or HLA Mismatched HSCT
	Affected / at Risk (%)	# Events
Total	6/26 (23.1%)
Cardiac disorders
Pericardial effusion	1/26 (3.8%)	1
Infections and infestations
Infection w.out neutropenia	4/26 (15.4%)	4
Infection with grade 3/4 neut	1/26 (3.8%)	1
Neutrophils/gran	1/26 (3.8%)	2
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/26 (3.8%)	1
Other (Not Including Serious) Adverse Events
	Rituximab Prophylaxis in TCD Unrelated or HLA Mismatched HSCT
	Affected / at Risk (%)	# Events
Total	23/26 (88.5%)
Gastrointestinal disorders
Nausea	2/26 (7.7%)	2
Vomiting	2/26 (7.7%)	2
General disorders
Fever	2/26 (7.7%)	3
Infections and infestations
Catheter-rel inf	4/26 (15.4%)	4
Infection w.out neutropenia	7/26 (26.9%)	10
Investigations
Alkaline phosphatase	5/26 (19.2%)	18
Bilirubin	2/26 (7.7%)	3
Hemoglobin (Hgb)	15/26 (57.7%)	28
Leukocytes	18/26 (69.2%)	100
Lymphopenia	18/26 (69.2%)	427
Neutrophils/gran	12/26 (46.2%)	61
Platelets	11/26 (42.3%)	62
SGOT (AST)	5/26 (19.2%)	7
SGPT (ALT)	10/26 (38.5%)	27
Metabolism and nutrition disorders
Hyperglycemia	2/26 (7.7%)	2
Hypoalbuminemia	3/26 (11.5%)	6
Hypocalcemia	7/26 (26.9%)	8
Hypokalemia	7/26 (26.9%)	9
Respiratory, thoracic and mediastinal disorders
Pneumonitis	2/26 (7.7%)	2
Vascular disorders
Hypotension	2/26 (7.7%)	2

Limitations/Caveats

[Not Specified]

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.