Treatment of Recurrent Primary or Secondary Central Nervous System (CNS) Lymphoma With ALIMTA (Pemetrexed)
The purpose of this research study is to determine the safety of the study drug pemetrexed, and the highest dose of this drug that can be given to people safely. Another goal of this research study is to gain information about how the body handles pemetrexed and how pemetrexed may work to treat the participant's lymphoma in the nervous system. Pemetrexed (also known as Alimta) has been approved by the FDA for the treatment of some lung cancers and has been shown to be effective in laboratory studies. Information from these studies suggests that pemetrexed may help to treat patients with either primary or secondary central nervous system lymphoma.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of the Treatment of Recurrent Primary or Secondary CNS Lymphoma With ALIMTA (Pemetrexed), a Novel Anti-Folate|
- To assess the safety and to determine the maximum tolerated dose of pemetrexed given intravenously for the treatment of recurrent lymphoma invading the CNS. [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]
- To determine the plasma pharmacokinetics of pemetrexed and assess drug penetration into the CSF. [ Time Frame: 6 and 1/2 years ] [ Designated as safety issue: No ]
- To provide preliminary evidence of pemetrexed activity against brain lymphoma my MRI criteria of clearance of CSF lymphoma cells. [ Time Frame: 6 years ] [ Designated as safety issue: No ]
- To identify the time to complete response. [ Time Frame: 6 years ] [ Designated as safety issue: No ]
- To provide a measure of reduction of enhancing tumor volume as compared to our nomogram of reduction of tumor volume for methotrexate recipients with brain lymphoma. [ Time Frame: 6 years ] [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Dose finding study
Given intravenously over a 10 to 20 minute period once every 14 days.
Other Name: Almita
- Since we are looking for the highest dose of pemetrexed that can be given to people safely, not everyone who participates in this study will be receiving the same amount of the study drug. The dose participants will receive will depend upon the number of people that have been enrolled on the study before them and how well they have tolerated their doses of the study drug.
- Pemetrexed is given into a vein (by IV) over a 10 to 20 minute period once every 14 days. This 14 day period is called a cycle of study treatment.
- Study treatment will be divided into three phases. Induction: Participants will be given a maximum of 8 cycles. If the participant does not achieve a complete response after eight induction cycles, they will be taken off study. A complete response means there is no evidence of disease on MRI or CT scan. Consolidation: If the participant has achieved complete response, they will have two additional cycles. Maintenance: Following the completion of the consolidation cycles, participants will receive the study drug only once per month. They can continue to receive maintenance cycles for up to a year from the start of the first induction cycle.
- Folic acid and vitamin B12 are two vitamins that have been shown to help lessen the severity of some side effects of pemetrexed. Participants will begin taking oral folic acid tablets at least 5 days before their first dose of pemetrexed and daily until 3 weeks after their last dose. Vitamin B12 is given through injections into your muscle. Participants will receive their first vitamin B12 injection 1-2 weeks before their first dose of pemetrexed. They will receive injections every 9 weeks.
- Corticosteroids such as dexamethasone have been shown to help prevent severe skin rashes associated with pemetrexed. Participants will receive dexamethasone twice daily starting the day before each pemetrexed infusion continuing until the day after each infusion.
- On day 1 of each cycle the following will be performed: a physical examination, blood work, vital signs, assessment of who well the participant is functioning, and mini-mental examination. On day 8 of each cycle blood work will be performed.
- Research blood work will be obtained (PKs) over the first four days of cycles 1 and 2 (or study participation days 1-4 and 15-18).
- Participants will come to the clinic once a month during the maintenance cycles for a physical examination, blood work, assessment of how well the participant is functioning, vital signs and mini-mental examination.
- Tumor assessments by MRI will be done after every 2 cycles during the induction and consolidation cycles. During the maintenance cycles the MRIs will be repeated every 2 cycles (once every 2 months).
- Collection of cerebral spinal fluid (CSF) for research tests will also likely be performed, if safe for you, to learn more about how well pemetrexed can cross the blood-brain barrier. This will be performed by one of two methods 6 and 24 hours after the pemetrexed is infused on days 1 and 2 of the first two cycles.
- After Alimta is given you will also receive, a white blood cell recruiting material, Neupogen to avoid suppressing your bone marrow.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00916630
|Contact: Jorg Dietrich, MD PhD MMSc||617-724-8770|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator: Jorg Dietrich, MD PhD MMSc|
|Beth Israel Deaconess Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator: Eric Wong|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator: Andrew Norden|
|Principal Investigator:||Jorg Dietrich, MD PhD MMSc||Massachusetts General Hospital|