Combined Immunochemotherapy Followed By Reduced Dose Radiation Therapy (RT) for Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00594815
• Collaborator: Northwestern Memorial Hospital (Other), Columbia University (Other), Kentuckiana Cancer Institute (Other), University of Virginia (Other), University of Vermont (Other)
• Enrollment: 52
• Location: 1
• Arm: 1
• Duration (Months): 161.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to find out if immunotherapy (rituximab) added to chemotherapy is a safe treatment for primary central nervous system lymphoma (PCNSL). PCNSL is a rare tumor. It is usually treated with chemotherapy and radiation. This combination prolongs survival, but about half of patients relapse. The investigators hope that the addition of rituximab will improve the control of the tumor.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Cytarabine, Leucovorin, Methotrexate, Procarbazine, Rituximab, Vincristine	N/A

Detailed Description

The purpose of this study is to find out if immunotherapy (rituximab) added to chemotherapy is a safe treatment for primary central nervous system lymphoma (PCNSL). PCNSL is a rare tumor. It is usually treated with chemotherapy and radiation. This combination prolongs survival, but about half of patients relapse. We hope that the addition of rituximab will improve the control of your tumor.

The second goal of this study is to assess a lower dose of brain radiation. Brain radiation may cause memory loss or dementia. For patients over the age of 60, the risk of significant memory loss is 80-90%. The risk for younger patients is smaller but less clear. In this, study patients whose tumors are in remission after chemotherapy will be treated with a lower dose of brain radiation. We hope that this lower dose will be less toxic. However, it is also possible that using a lower dose of radiation will be less effective in controlling your tumor.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Combined Immunochemotherapy Followed by Reduced Dose RT for Patients With Newly Diagnosed Primary Central Nervous System Lymphoma
• Study Start Date: Aug 28, 2002
• Actual Primary Completion Date: Feb 23, 2016
• Actual Study Completion Date: Feb 23, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Cytarabine, Leucovorin, Methotrexate, Procarbazine, Rituximab, Vincristine; Immunochemotherapy

Outcome Measures

Primary Outcome Measures

1. Total Number of Participants Who Experienced Acute Treatment Related Adverse Events [2 years]

   The toxicity of this combined regimen will be measured using the NCI CTC version 2.0.

2. Progression Free Survival [2 Years]

   Overall Progression Free Survival at 2 years

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• All patients must have a histologic diagnosis of non-Hodgkin's lymphoma by brain biopsy. Patients who have an inconclusive biopsy or who are not candidates for biopsy may be eligible provided they have a typical cranial magnetic resonance imaging (MRI) or computed tomography (CT) scan and meet at least one of the following two criteria:

• A positive cerebrospinal fluid (CSF) cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers

• A biopsy of the vitreous or uvea demonstrating non-Hodgkin's lymphoma

• A typical MRI/CT scan for primary intracranial lymphoma is defined as the presence of hypo, iso, or hyperdense parenchymal contrast-enhancing (usually homogeneously) mass lesion(s)

• Patients must be HIV-1 negative

• Patients must have a normal or negative pre-treatment systemic evaluation including:

• A bone marrow aspirate and biopsy

• CT scans of the chest, abdomen and pelvis

• Patients must have adequate bone marrow function (defined as peripheral leucocyte count > 4000 cells/mm3 and platelet count > 100,000 cells/mm3), liver function (bilirubin < 2.0 mg and SGOT < 2 times upper limit of normal), and adequate renal function (serum creatinine < 1.5 mg/dl or creatinine clearance > 50 cc/min/1.73M2)

• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment

Exclusion Criteria:

The following would exclude a patient from the study:

• Prior cranial irradiation

• Other active primary malignancy with the exception of basal cell carcinoma of the skin and cervical carcinoma in situ

• Pre-existing immunodeficiency such as renal transplant recipient

• Prior treatment with chemotherapy for CNS lymphoma

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
• Northwestern Memorial Hospital
• Columbia University
• Kentuckiana Cancer Institute
• University of Virginia
• University of Vermont

Investigators

• Principal Investigator: Antonio Omuro, 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: NCT00594815
• Other Study ID Numbers: 01-146; NCT00059956
• First Posted: Jan 16, 2008
• Last Update Posted: Apr 6, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Memorial Sloan Kettering Cancer Center: Lymphoma; Central Nervous System
• Additional relevant MeSH terms: Lymphoma; Leucovorin; Cytarabine; Rituximab; Methotrexate; Vincristine; Procarbazine

Study Results

Participant Flow

Recruitment Details	Protocol Open to Accrual 08/08/2002 Protocol Closed to Accrual 03/10/2009 Primary Completion Date 02-23-2016 Recruitment Location is the medical clinic

Arm/Group Title	Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma
Arm/Group Description	Cytarabine, Leucovorin, Methotrexate, Procarbazine, Rituximab, Vincristine: Immunochemotherapy
Period Title: Overall Study
STARTED	52
COMPLETED	43
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma
Arm/Group Description	Cytarabine, Leucovorin, Methotrexate, Procarbazine, Rituximab, Vincristine: Immunochemotherapy
Overall Participants	52
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	34 65.4%
>=65 years	18 34.6%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	60
Sex: Female, Male (Count of Participants)
Female	22 42.3%
Male	30 57.7%

Outcome Measures

1. Primary Outcome

Title	Total Number of Participants Who Experienced Acute Treatment Related Adverse Events
Description	The toxicity of this combined regimen will be measured using the NCI CTC version 2.0.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma
Arm/Group Description	Cytarabine, Leucovorin, Methotrexate, Procarbazine, Rituximab, Vincristine: Immunochemotherapy
Measure Participants	52
Count of Participants [Participants]	52 100%

2. Primary Outcome

Title	Progression Free Survival
Description	Overall Progression Free Survival at 2 years
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma
Arm/Group Description	Cytarabine, Leucovorin, Methotrexate, Procarbazine, Rituximab, Vincristine: Immunochemotherapy
Measure Participants	52
Number (95% Confidence Interval) [percentage of participants]	57 109.6%

Adverse Events

Time Frame	Every other week during treatment cycles. Follow up evaluation will be assessed every 3 months for the first year after completing treatment. Follow up will then be done every 4 months for the second year, every 6 months until the 5th year and then annually.
Arm/Group Title	Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma
Arm/Group Description	This is a single-armed pilot study designed to evaluate the safety and efficacy of combined immunochemotherapy followed by reduced dose radiation for participants with newly diagnosed PCNSL.
All Cause Mortality
	Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma
	Affected / at Risk (%)	# Events
Total	13/52 (25%)
Serious Adverse Events
	Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma
	Affected / at Risk (%)	# Events
Total	22/52 (42.3%)
Blood and lymphatic system disorders
Leukocytes	4/52 (7.7%)
Cardiac disorders
Hypotension	2/52 (3.8%)
Eye disorders
Vision-double vision	1/52 (1.9%)
Gastrointestinal disorders
Dehydration	1/52 (1.9%)
Duodenal ulcer	1/52 (1.9%)
Radiation mucositis	1/52 (1.9%)
Nausea	1/52 (1.9%)
Vomiting	1/52 (1.9%)
General disorders
Fever	2/52 (3.8%)
Pain, other	1/52 (1.9%)
Infections and infestations
Febrile neutropenia	3/52 (5.8%)
Infection without neutropenia	4/52 (7.7%)
Infection	1/52 (1.9%)
Wound, infectious	3/52 (5.8%)
Investigations
Neutrophils/granulocytes	4/52 (7.7%)
Platelets	4/52 (7.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/52 (1.9%)
Nervous system disorders
Ataxia	1/52 (1.9%)
Neurology, other	2/52 (3.8%)
Psychiatric disorders
Hallucinations	1/52 (1.9%)
Mood alteration-anxiety	1/52 (1.9%)
Mood alteration - depression	1/52 (1.9%)
Personality/behavior	1/52 (1.9%)
Renal and urinary disorders
Elevated Creatinine	1/52 (1.9%)
Renal failure	1/52 (1.9%)
Renal/GU, other	1/52 (1.9%)
Respiratory, thoracic and mediastinal disorders
Cough	1/52 (1.9%)
Pulmonary, other	1/52 (1.9%)
Vascular disorders
Thrombosis	1/52 (1.9%)
Other (Not Including Serious) Adverse Events
	Immunocompetent Pts With Newly Diagnosed Primary CNS Lymphoma
	Affected / at Risk (%)	# Events
Total	43/52 (82.7%)
Blood and lymphatic system disorders
Hemoglobin/Anemia	33/52 (63.5%)
Gastrointestinal disorders
Constipation	5/52 (9.6%)
General disorders
Fatigue	4/52 (7.7%)
Hepatobiliary disorders
Bilirubin	5/52 (9.6%)
Immune system disorders
Leukocytes	31/52 (59.6%)
Lymphopenia	30/52 (57.7%)
Investigations
SGPT (ALT)	24/52 (46.2%)
Neutrophils/granulocytes	22/52 (42.3%)
SGOT (AST)	16/52 (30.8%)
Platelets	14/52 (26.9%)
PT	9/52 (17.3%)
PTT	6/52 (11.5%)
Metabolism and nutrition disorders
Hypocalcemia	36/52 (69.2%)
Hyperglycemia	36/52 (69.2%)
Hypophosphatemia	10/52 (19.2%)
Hypoalbuminemia	8/52 (15.4%)
Hyponatremia	7/52 (13.5%)
Hypokalemia	7/52 (13.5%)
Hypoglycemia	4/52 (7.7%)
Hyperkalemia	3/52 (5.8%)
Nervous system disorders
Neuropathy-sensory	3/52 (5.8%)
Renal and urinary disorders
Creatinine	6/52 (11.5%)

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.