Chemotherapeutic Agent ToxicityPhase 1/2NCT00727831
Methotrexate, Glucarpidase, and Leucovorin in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma
A Phase 1/2 study testing glucarpidase, leucovorin calcium and methotrexate in people with Chemotherapeutic Agent Toxicity and Lymphoma, run by University College, London at 2 sites in United Kingdom.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as methotrexate and leucovorin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Glucarpidase may help return the level of methotrexate in the blood to a safe range. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chemotherapeutic Agent Toxicity, Lymphoma, Mucositis
- What is being tested?
- glucarpidase, leucovorin calcium and methotrexate
- Type of treatment
- Surgery or procedure
- How many people
- 4 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Jul 2008to Jul 2011
- Phase
- Phase 1/2
- 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
- ECOG performance status 0-3
- Neutrophils ≥ 1 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Bilirubin < 1.5 times upper limit of normal
- Glomerular filtration rate (initially measured by EDTA/isotope method) ≥ 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after completion of study therapy
Who cannot join
- HIV positivity
- Dementia or neurological dysfunction not considered to be due to the PCNSL
- Other serious or uncontrolled medical conditions
- Prior malignancy, except adequately treated nonmelanoma skin cancer or carcinoma in situ
- PRIOR CONCURRENT THERAPY:
- No prior cytotoxic chemotherapy
- No concurrent prophylactic antibiotics
- No concurrent co-trimoxazole
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Leeds General Infirmary
Leeds, England, LS1 3EX
Torbay Hospital
Torquay, England, TQ2 7AA
About this study
Official title: Phase I Trial of Escalating High Dose Methotrexate Supported by Glucarpidase to Treat Patients With Primary Central Nervous Lymphoma (PCNSL)
RATIONALE: Drugs used in chemotherapy, such as methotrexate and leucovorin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Glucarpidase may help return the level of methotrexate in the blood to a safe range. Giving high-dose methotrexate together with glucarpidase and leucovorin may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of methotrexate when given together with glucarpidase and leucovorin in treating patients with newly diagnosed primary central nervous system lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- To determine the dose-limiting toxicity of methotrexate (MTX) when given in combination with glucarpidase in patients with newly diagnosed primary CNS lymphoma (PCNSL).
- To determine the incidence of immediate reactions related to the use of glucarpidase in these patients.
- To define a safer, more practical, and simpler regimen for delivering multiple courses of high-dose MTX using glucarpidase and 'short' leucovorin calcium rescue in these patients.
- To monitor quality of life and mental function during and after therapy in these patients.
Secondary
- To use this regimen as a platform for phase III studies in PCNSL.
- To record disease response, duration of response, and overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of high-dose methotrexate (HD-MTX).
Patients receive HD-MTX IV over 4 hours on day 1. Beginning 22 hours after the start of HD-MTX, patients receive glucarpidase IV over 15 minutes on day 2 followed by leucovorin calcium orally or IV on days 2-7. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Within 2-4 weeks after completion of study treatment, patients achieving maximum response are stratified according to age (< 60 years vs ≥ 60 years) and may undergo whole brain radiotherapy (WBRT) once daily, 5 days a week, for 3 to 5 weeks.
Patients undergo blood sample collection periodically to assess glucarpidase antibodies and MTX levels.
Patients are assessed for mucositis incidence and severity periodically, and complete quality of life assessments using the EORTC QLQ-30 questionnaire and the Mini-Mental State questionnaire at baseline, during, and after completion of study.
After completion of study treatment, patients are followed at 6 weeks after WBRT, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
- Conditions
- Chemotherapeutic Agent Toxicity, Lymphoma, Mucositis, Neurotoxicity
- Being tested
- glucarpidase, leucovorin calcium, methotrexate, laboratory biomarker analysis, quality-of-life assessment
- Keywords
- neurotoxicity, chemotherapeutic agent toxicity, mucositis, primary central nervous system non-Hodgkin lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage I adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma
- Medical subject headings
- Lymphoma, Mucositis, Neurotoxicity Syndromes, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
glucarpidaseDrug
methotrexateDrug
laboratory biomarker analysisOther
quality-of-life assessmentProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Immediate toxicity (incidence of reactions to glucarpidase) as determined by the NCI CTC
Incidence and severity of renal dysfunction as determined by the NCI CTC
Incidence and severity of mucositis as determined by the NCI CTC and WHO mucositis grading scale
Incidence and severity of CNS toxicity and neurocognitive changes taken from patients' medical records and measured using the Mini-Mental State questionnaire and MRI data
Secondary outcomes (8)
Hematological toxicity (i.e., number of courses of therapy associated with neutrophils < 0.5 x 10e9/L or platelets < 50 x 10e9/L as measured by routine blood counts)
Incidence of infection (i.e., number of days with fever ≥ 38 C° measured by clinical examination and days of intravenous antibiotics taken from patients' medical records)
Number of inpatient days taken from patients' medical records
Disease response and remission rates measured by serial MRI scanning (and eye examination and lumbar puncture if necessary)
Disease outcome, time to progression, and overall survival at 2 years from start of therapy measured by clinical examination and serial MRI scanning
Relative dose intensity
Methotrexate levels post-glucarpidase (expressed as a clinically important reduction, which is defined as a methotrexate level of < 1 μmol/L in all post-glucarpidase samples)
Incidence of antibodies to glucarpidase measured serologically at the start of each methotrexate course and at follow-up visits if present during therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2008 (estimated)
- Study startJul 2008
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chemotherapeutic Agent ToxicityStudies of the same condition, open and under way.
- More trials run by University College, LondonThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK
- Responsible party
- Sponsor
- Investigators
- Roderick Johnson, MD, Principal investigator, Leeds General Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00727831
- Sponsor's protocol ID
- CDR0000599206
- Other IDs
- CRUK-BRD/07/004, 2007-002570-58, EU-20861
- Status last verified
- Jan 2014
- First submitted
- 1 Aug 2008
- Last updated
- 27 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Escalating High Dose Methotrexate Supported by Glucarpidase to Treat Patients With Primary Central Nervous Lymphoma (PCNSL)
- ClinicalTrials.gov ID
- NCT00727831
- Acronym / sponsor ID
- CDR0000599206
- Conditions
- Chemotherapeutic Agent Toxicity, Lymphoma, Mucositis, Neurotoxicity
- Keywords
- neurotoxicity, chemotherapeutic agent toxicity, mucositis, primary central nervous system non-Hodgkin lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage I adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Cancer Research UK
- Study start
- Jul 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 4 Aug 2008 (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.
RATIONALE: Drugs used in chemotherapy, such as methotrexate and leucovorin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Glucarpidase may help return the level of methotrexate in the blood to a safe range. Giving high-dose methotrexate together with glucarpidase and leucovorin may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of methotrexate when given together with glucarpidase and leucovorin in treating patients with newly diagnosed primary central nervous system lymphoma.
Detailed description
OBJECTIVES:
Primary
- To determine the dose-limiting toxicity of methotrexate (MTX) when given in combination with glucarpidase in patients with newly diagnosed primary CNS lymphoma (PCNSL).
- To determine the incidence of immediate reactions related to the use of glucarpidase in these patients.
- To define a safer, more practical, and simpler regimen for delivering multiple courses of high-dose MTX using glucarpidase and 'short' leucovorin calcium rescue in these patients.
- To monitor quality of life and mental function during and after therapy in these patients.
Secondary
- To use this regimen as a platform for phase III studies in PCNSL.
- To record disease response, duration of response, and overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of high-dose methotrexate (HD-MTX).
Patients receive HD-MTX IV over 4 hours on day 1. Beginning 22 hours after the start of HD-MTX, patients receive glucarpidase IV over 15 minutes on day 2 followed by leucovorin calcium orally or IV on days 2-7. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Within 2-4 weeks after completion of study treatment, patients achieving maximum response are stratified according to age (< 60 years vs ≥ 60 years) and may undergo whole brain radiotherapy (WBRT) once daily, 5 days a week, for 3 to 5 weeks.
Patients undergo blood sample collection periodically to assess glucarpidase antibodies and MTX levels.
Patients are assessed for mucositis incidence and severity periodically, and complete quality of life assessments using the EORTC QLQ-30 questionnaire and the Mini-Mental State questionnaire at baseline, during, and after completion of study.
After completion of study treatment, patients are followed at 6 weeks after WBRT, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- ECOG performance status 0-3
- Neutrophils ≥ 1 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Bilirubin < 1.5 times upper limit of normal
- Glomerular filtration rate (initially measured by EDTA/isotope method) ≥ 50 mL/min
Key exclusion criteria (8 listed)
- HIV positivity
- Dementia or neurological dysfunction not considered to be due to the PCNSL
- Other serious or uncontrolled medical conditions
- Prior malignancy, except adequately treated nonmelanoma skin cancer or carcinoma in situ
- No prior cytotoxic chemotherapy
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 |
|---|---|---|
| glucarpidase | Drug | – |
| leucovorin calcium | Drug | – |
| methotrexate | Drug | – |
| laboratory biomarker analysis | Other | – |
| quality-of-life assessment | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Immediate toxicity (incidence of reactions to glucarpidase) as determined by the NCI CTC
Incidence and severity of renal dysfunction as determined by the NCI CTC
Incidence and severity of mucositis as determined by the NCI CTC and WHO mucositis grading scale
Incidence and severity of CNS toxicity and neurocognitive changes taken from patients' medical records and measured using the Mini-Mental State questionnaire and MRI data
8 secondary outcomes
Hematological toxicity (i.e., number of courses of therapy associated with neutrophils < 0.5 x 10e9/L or platelets < 50 x 10e9/L as measured by routine blood counts)
Incidence of infection (i.e., number of days with fever ≥ 38 C° measured by clinical examination and days of intravenous antibiotics taken from patients' medical records)
Number of inpatient days taken from patients' medical records
Disease response and remission rates measured by serial MRI scanning (and eye examination and lumbar puncture if necessary)
Disease outcome, time to progression, and overall survival at 2 years from start of therapy measured by clinical examination and serial MRI scanning
Relative dose intensity
Methotrexate levels post-glucarpidase (expressed as a clinically important reduction, which is defined as a methotrexate level of < 1 μmol/L in all post-glucarpidase samples)
Incidence of antibodies to glucarpidase measured serologically at the start of each methotrexate course and at follow-up visits if present during therapy
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 27 Jan 2014.
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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.
Roderick Johnson, MD principal investigator
Leeds General Infirmary
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing glucarpidase, leucovorin calcium and methotrexate in people with Chemotherapeutic Agent Toxicity and Lymphoma, run by University College, London at 2 sites in United Kingdom.
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 8 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 27 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Immediate toxicity (incidence of reactions to glucarpidase) as determined by the NCI CTC. The study lists 4 primary outcomes in all. 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 27 Jan 2014.