Central Nervous System LymphomaPhase 1NCT00916630
Treatment of Recurrent Primary or Secondary Central Nervous System (CNS) Lymphoma With ALIMTA (Pemetrexed)
A Phase 1 study testing pemetrexed in people with Central Nervous System Lymphoma, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Central Nervous System Lymphoma
- What is being tested?
- pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2009to Sep 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Disease state (5 categories of patients with these extremely rare disease are eligible: 1) Patients intolerant of Methotrexate-must have a diagnosis of B cell non-Hodgkin's lymphoma 2) Patients unable to receive methotrexate due to lack of drug availability-must have a diagnosis of B cell non-Hodgkin's lymphoma 3) Patients who fail to achieve a complete response to initial therapy for primary CNS lymphoma-must have a diagnosis of B cell non-Hodgkin's lymphoma 4) Recurrent Primary CNS lymphoma-If in the judgement of the treating physician therapy would be initiated without a repeat biopsy then the original biopsy with a diagnosis of B cell non-Hodgkin's lymphoma will suffice 5) Secondary CNS lymphoma-If in the judgement of the treating physician therapy would be initiated without a repeat biopsy then the original biopsy with a histologic diagnosis of B cell non-Hodgkin's lymphoma will suffice.
- Histologic diagnosis of B cell non-Hodgkin's lymphoma with measurable disease OR cytologic diagnosis of B cell non-Hodgkin's lymphoma with measurable disease OR immunohistochemical diagnosis of monoclonality (CDF) with or without measurable intracranial disease OR molecular diagnostic diagnosis of monoclonality CSF) with or without measurable intracranial disease OR Ocular-patients may have a combination of histologic confirmation of ocular lymphoma and measurable intracranial tumor. Slit-lamp examination and vitreal or retinal biopsy will be done to confirm ocular lymphoma OR neurolymphomatosis-evidence of measurable disease as nerve seeking lymphoma on MRI imaging with histologic diagnosis at any site.
- Karnofsky score of 60 or greater
- Must be able to undergo MRI scanning
- 18 years of age or older
- Life expectancy of at least 2 months
- Laboratory values as outlined in protocol
- Must be willing to practice an effective method of birth control during participation in the study whether male or female.
Who cannot join
- Definitive histologic diagnosis of low grade lymphoma without substantive clinical suspicion of transformation to an aggressive lymphoma
- Renal dysfunction defined as creatinine clearance < 45 ml/min or serum creatinine > 2mg/dL
- Transaminases > 3 times above the upper limits of the institutional normal
- Acute infection, granulocytopenia or medical condition precluding surgery as judged by the caring physician and review team
- Pregnant or lactating females
- Patients must not have pre-existing immunosuppression, concurrent immunosuppressive treatment (with the exception of dexamethasone) or be a transplant recipient
Show all 11Show fewer
- Patients must not have received prior whole brain irradiation. They can have received prior focal irradiation
- Prior participation in chemotherapy, cytotoxic therapy, immunotherapy or therapeutic protocols within 4 weeks fo enrollment. Patients unable to stop NSAIDS or Cox 2 inhibitors for two day before and after treatment as well as the day of treatment
- No other active systemic malignancy with the exception of basal cell carcinoma of the skin and cervical carcinoma in situ. Patients with a remote history (5 years or more) of malignancy are eligible for the protocol in the absence of active disease
- Clinically relevant third space fluid collection refractory to drainage
- Patient refusal to participate in the pK study
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase I Study of the Treatment of Recurrent Primary or Secondary CNS Lymphoma With ALIMTA (Pemetrexed), a Novel Anti-Folate
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.
Read the detailed description
- 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.
- Conditions
- Central Nervous System Lymphoma
- Being tested
- pemetrexed
- Keywords
- recurrent, alimta, pemetrexed, CNS lymphoma, Primary CNS lymphoma, Metastatic lymphoma to brain
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pemetrexedDrug
Also called Almita
Given intravenously over a 10 to 20 minute period once every 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Single-arm treatment | Other | Dose finding study Receives: Drug: pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and to determine the maximum tolerated dose of pemetrexed given intravenously for the treatment of recurrent lymphoma invading the CNS.
Measured: 6 years
Secondary outcomes (4)
To determine the plasma pharmacokinetics of pemetrexed and assess drug penetration into the CSF.
Measured: 6 and 1/2 years
To provide preliminary evidence of pemetrexed activity against brain lymphoma my MRI criteria of clearance of CSF lymphoma cells.
Measured: 6 years
To identify the time to complete response.
Measured: 6 years
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.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2009 (estimated)
- Study startJan 2009
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System LymphomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Eli Lilly and Company, Dana-Farber Cancer Institute
- Responsible party
- Principal investigator, Jorg Dietrich, M.D., Ph.D., Massachusetts General Hospital
- Investigators
- Jorg Dietrich, MD PhD MMSc, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00916630
- Sponsor's protocol ID
- 06-097
- Other IDs
- H3-US-X059
- Status last verified
- Sep 2015
- First submitted
- 5 Jun 2009
- Last updated
- 23 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Treatment of Recurrent Primary or Secondary CNS Lymphoma With ALIMTA (Pemetrexed), a Novel Anti-Folate
- ClinicalTrials.gov ID
- NCT00916630
- Acronym / sponsor ID
- 06-097
- Conditions
- Central Nervous System Lymphoma
- Keywords
- recurrent, alimta, pemetrexed, CNS lymphoma, Primary CNS lymphoma, Metastatic lymphoma to brain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Eli Lilly and Company, Dana-Farber Cancer Institute
- Study start
- Jan 2009
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 9 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single-arm treatment | Other | Drug: pemetrexedDose finding study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Disease state (5 categories of patients with these extremely rare disease are eligible: 1) Patients intolerant of Methotrexate-must have a diagnosis of B cell non-Hodgkin's lymphoma 2) Patients unable to receive methotrexate due to lack of drug availability-must have a diagnosis of B cell non-Hodgkin's lymphoma 3) Patients who fail to achieve a complete response to initial therapy for primary CNS lymphoma-must have a diagnosis of B cell non-Hodgkin's lymphoma 4) Recurrent Primary CNS lymphoma-If in the judgement of the treating physician therapy would be initiated without a repeat biopsy then the original biopsy with a diagnosis of B cell non-Hodgkin's lymphoma will suffice 5) Secondary CNS lymphoma-If in the judgement of the treating physician therapy would be initiated without a repeat biopsy then the original biopsy with a histologic diagnosis of B cell non-Hodgkin's lymphoma will suffice.
- Histologic diagnosis of B cell non-Hodgkin's lymphoma with measurable disease OR cytologic diagnosis of B cell non-Hodgkin's lymphoma with measurable disease OR immunohistochemical diagnosis of monoclonality (CDF) with or without measurable intracranial disease OR molecular diagnostic diagnosis of monoclonality CSF) with or without measurable intracranial disease OR Ocular-patients may have a combination of histologic confirmation of ocular lymphoma and measurable intracranial tumor. Slit-lamp examination and vitreal or retinal biopsy will be done to confirm ocular lymphoma OR neurolymphomatosis-evidence of measurable disease as nerve seeking lymphoma on MRI imaging with histologic diagnosis at any site.
- Karnofsky score of 60 or greater
- Must be able to undergo MRI scanning
- 18 years of age or older
Key exclusion criteria (11 listed)
- Definitive histologic diagnosis of low grade lymphoma without substantive clinical suspicion of transformation to an aggressive lymphoma
- Renal dysfunction defined as creatinine clearance < 45 ml/min or serum creatinine > 2mg/dL
- Transaminases > 3 times above the upper limits of the institutional normal
- Acute infection, granulocytopenia or medical condition precluding surgery as judged by the caring physician and review team
- Pregnant or lactating females
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pemetrexedAlso: AlmitaGiven intravenously over a 10 to 20 minute period once every 14 days. | Drug | Single-arm treatment |
Primary outcome
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
4 secondary outcomes
To determine the plasma pharmacokinetics of pemetrexed and assess drug penetration into the CSF.
Time frame: 6 and 1/2 years
To provide preliminary evidence of pemetrexed activity against brain lymphoma my MRI criteria of clearance of CSF lymphoma cells.
Time frame: 6 years
To identify the time to complete response.
Time frame: 6 years
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorg Dietrich, MD PhD MMSc principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing pemetrexed in people with Central Nervous System Lymphoma, run by Massachusetts General Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2015.