PCNSL: Rituximab, Methotrexate, Procarbazine and Vincristine Followed by High-dose Chemotherapy With Autologous Stem-cell Rescue in Newly-diagnosed Primary CNS Lymphoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00596154

Collaborator

(none)

Enrollment

Locations

Arm

216

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety of this new treatment offered in this study. PCNSL can be cured in less than half of patients with standard treatment, a combination of chemotherapy and brain radiation. Also, the combination of chemotherapy and brain radiation may result in serious lasting side effects. Most patients older than age 60 develop memory problems, difficulty walking or inability to control their bladder. Some patients younger than age 60 also develop these side effects.

Condition or Disease	Intervention/Treatment	Phase
CNS Lymphoma CNS Brain Cancer Non-Hodgkin's Lymphoma	Other: Rituximab, Methotrexate, Vincristine, Procarbazine, PBPCs collection, Busulfan, Thiotepa, and Cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Rituximab, Methotrexate, Procarbazine and Vincristine Followed by High-dose Chemotherapy With Autologous Stem-cell Rescue in Newly-diagnosed Primary CNS Lymphoma (PCNSL)

Actual Study Start Date :

Dec 1, 2004

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Rituximab, methotrexate (MTX), procarbazine and vincristine (R-MPV). The peripheral blood stem cell (PBSC) harvest procedure will be performed at the discretion of the hematology attending (usually after the 1st or 2nd cycle of R-MPV)and high dose chemotherapy Busulfan, Thiotepa, and Cyclophosphamide. Patients will be off study at the time of death. All patients will be followed for survival every 6 months throughout their lifetime. Survival status may be obtained by phone call, clinical visit or medical records (e.g. physician notes/laboratory results of clinic or hospital visit.	Other: Rituximab, Methotrexate, Vincristine, Procarbazine, PBPCs collection, Busulfan, Thiotepa, and Cyclophosphamide The initial treatment will consist of cycles of 14 days. Each cycle will start with rituximab, which will be given by vein on day 1. On day 2 you will be admitted to the hospital and will receive 3 other drugs: Methotrexate will be given by vein over 2 to 3 hours only on day 2. Vincristine will be given as a single injection over a few minutes only on day 2. Procarbazine is a pill that you will take at bedtime for 7 nights starting on day 2. Procarbazine is only given every other cycle. Other Names: During each cycle, you will receive Rituximab typically as an outpatient on day 1 and then be admitted on day 2 to receive the other chemotherapy. You will be in the hospital for about 5 days and will be re-admitted to the hospital about 9 days later to start the next cycle. After each cycle of chemotherapy you will take a medicine called G-CSF to protect you against infection. PBPCs will be collected when determined by your doctor and may occur with cycle 1 or cycle 2. You will be admitted again for the high-dose chemotherapy and will receive supportive medications to help avoid complications, including antibiotics and blood transfusions. Three drugs, Busulfan, Thiotepa, and Cyclophosphamide will be given to you over 8 days. After a rest period of approximately 1-2 days, we will give your PBPCs (or bone marrow) back to you by vein. You will be in the hospital for at least 3 weeks.

Arm

Intervention/Treatment

Experimental: 1

Rituximab, methotrexate (MTX), procarbazine and vincristine (R-MPV). The peripheral blood stem cell (PBSC) harvest procedure will be performed at the discretion of the hematology attending (usually after the 1st or 2nd cycle of R-MPV)and high dose chemotherapy Busulfan, Thiotepa, and Cyclophosphamide. Patients will be off study at the time of death. All patients will be followed for survival every 6 months throughout their lifetime. Survival status may be obtained by phone call, clinical visit or medical records (e.g. physician notes/laboratory results of clinic or hospital visit.

Other: Rituximab, Methotrexate, Vincristine, Procarbazine, PBPCs collection, Busulfan, Thiotepa, and Cyclophosphamide

The initial treatment will consist of cycles of 14 days. Each cycle will start with rituximab, which will be given by vein on day 1. On day 2 you will be admitted to the hospital and will receive 3 other drugs: Methotrexate will be given by vein over 2 to 3 hours only on day 2. Vincristine will be given as a single injection over a few minutes only on day 2. Procarbazine is a pill that you will take at bedtime for 7 nights starting on day 2. Procarbazine is only given every other cycle.

Other Names:

During each cycle, you will receive Rituximab typically as an outpatient on day 1 and then be

admitted on day 2 to receive the other chemotherapy. You will be in the hospital for about 5 days and will be re-admitted to the hospital about 9 days

later to start the next cycle. After each cycle of chemotherapy you will take a medicine called G-CSF to protect you against

infection. PBPCs will be collected when determined by your doctor and may occur with cycle 1 or cycle 2.

You will be admitted again for the high-dose chemotherapy and will receive supportive

medications to help avoid complications, including antibiotics and blood transfusions. Three

drugs, Busulfan, Thiotepa, and Cyclophosphamide will be given to you over 8 days. After a

rest period of approximately 1-2 days, we will give your PBPCs (or bone marrow) back to you

by vein. You will be in the hospital for at least 3 weeks.

Outcome Measures

Primary Outcome Measures

to evaluate the safety and efficacy of the use of R-MPV followed by high-dose chemotherapy using thiotepa, cyclophosphamide and busulfan with stem cell rescue in patients with newly diagnosed PCSNL. [1-year event-free survival and acute treatment-related toxicity.]

Secondary Outcome Measures

to evaluate response rates with the combination of rituximab and MPV as induction chemotherapy. [after 5 cycles]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 72 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All patients must have non-Hodgkin's lymphoma involving the brain, as demonstrated by CT or MRI and histologic confirmation by one of the following: A positive 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. Brain biopsy.

Patients must be HIV-1 negative.
Patient must have left ventricular ejection fraction ≥ 50%.
Patients must have no evidence of systemic lymphoma. This must be demonstrated by a CT scan of the chest, abdomen and pelvis prior to registration.
Patients must have adequate bone marrow function (defined as peripheral leucocyte count >3000 cells/mm3 and platelet count > 100,000 cells/mm3), liver function (bilirubin < 2.0 mg%), and adequate renal function (serum creatinine < 1.5 mg/dl or creatinine clearance > 50cc/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.
Patients must be between 18 and 72 years-old.
Patients must sign an informed consent.

Exclusion Criteria:

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 Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065