Ignite Creation Date:
2024-05-05 @ 12:11 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00267865
Status:
COMPLETED
Last Update Posted:
2020-06-01
First Post:
2005-12-21
Brief Title:
Chemotherapy and HAART to Treat AIDS-related Primary Brain Lymphoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
AIDS-Related Primary Central Nervous System Lymphoma A Phase II Pilot Study of High-Dose Intravenous Methotrexate With Rituximab Leucovorin Rescue and Highly Active Antiretroviral Therapy
Status:
COMPLETED
Status Verified Date:
2020-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will investigate the use of chemotherapy plus highly active antiretroviral therapy HAART in patients with Acquired Immunodeficiency Syndrome AIDS-related primary brain lymphoma None of the drugs used in this study are experimental but chemotherapy plus HAART has not been established as a standard treatment in patients with AIDS The chemotherapy regimen used in this study see below was chosen because it may be less toxic to immune cells called T-lymphocytes than most drug treatments for lymphoma
People with AIDS 18 and older and have primary brain lymphoma may be eligible for this study Candidates are screened with a medical history and physical examination magnetic resonance imaging MRI computed tomography CT and positron emission tomography PET scans cerebrospinal fluid studies brain biopsy at tumor sites if possible electrocardiogram and blood tests
Participants undergo six 2-week induction treatment cycles of HAART plus chemotherapy with methotrexate rituximab and leucovorin followed by two 4-week consolidation treatment cycles using HAART methotrexate and leucovorin and then HAART alone Rituximab is given by intravenous intravenous IV through a vein day 1 of each cycle Also on day 1 IV fluids are given to lower acidity in the urine to protect the kidneys from the methotrexate On day 2 methotrexate is infused through a vein over 4 hours Starting 24 hours after initiation of the methotrexate infusion leucovorin is given every 3 to 6 hours first IV and then possibly by mouth until the drug decreases to a target level in the blood HAART is begun as soon as possible The specific HAART regimen for each patient is determined individually All patients are hospitalized the first week of every 2-week treatment cycle for safety monitoring In addition to HAART and chemotherapy patients undergo the following tests and procedures
Intellectual functioning Before starting treatment patients are tested for their ability to understand basic concepts and coordination in order to be able to evaluate how the brain lymphoma affects thinking and concentration After the lymphoma appears to have resolved more formal and intensive tests are done The intensive tests are repeated each year and shorter interim tests are done about every 6 months Also a specialist periodically monitors patients understanding of HAART and the importance of this therapy
Blood tests Blood is drawn every day during hospitalizations to measure methotrexate levels and to evaluate kidney and liver function and blood counts Blood is also drawn before starting therapy when the lymphoma disappears 6 months after completing treatment and any time it appears that the lymphoma may have recurred to test for Epstein-Barr virus EBV a virus that is almost always present in AIDS-related primary brain lymphoma
Imaging tests Patients undergo magnetic resonance imaging MRI and positron emission tomography PET scans periodically to monitor the effects of treatment on the lymphoma MRI scans are done after the 2nd 4th 6th and 8th treatments then every 2 months for three times every 3 months for six times every 6 months for four times and then every year for 5 years or sooner if there is a concern about the brain PET scans are done after the first cycle after the MRI suggests the lymphoma is gone and then yearly
Lumbar puncture spinal tap This test is done to look for EBV in the cerebrospinal fluid CSF Under local anesthetic a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord and a small amount of fluid is collected through the needle This test is done at the same times as the blood tests for EBV
Eye examinations Patients eyes are examined periodically because brain lymphoma can sometimes spread to the eye and because some people with AIDS-related primary brain lymphoma are at risk of certain eye infections
People with AIDS 18 and older and have primary brain lymphoma may be eligible for this study Candidates are screened with a medical history and physical examination magnetic resonance imaging MRI computed tomography CT and positron emission tomography PET scans cerebrospinal fluid studies brain biopsy at tumor sites if possible electrocardiogram and blood tests
Participants undergo six 2-week induction treatment cycles of HAART plus chemotherapy with methotrexate rituximab and leucovorin followed by two 4-week consolidation treatment cycles using HAART methotrexate and leucovorin and then HAART alone Rituximab is given by intravenous intravenous IV through a vein day 1 of each cycle Also on day 1 IV fluids are given to lower acidity in the urine to protect the kidneys from the methotrexate On day 2 methotrexate is infused through a vein over 4 hours Starting 24 hours after initiation of the methotrexate infusion leucovorin is given every 3 to 6 hours first IV and then possibly by mouth until the drug decreases to a target level in the blood HAART is begun as soon as possible The specific HAART regimen for each patient is determined individually All patients are hospitalized the first week of every 2-week treatment cycle for safety monitoring In addition to HAART and chemotherapy patients undergo the following tests and procedures
Intellectual functioning Before starting treatment patients are tested for their ability to understand basic concepts and coordination in order to be able to evaluate how the brain lymphoma affects thinking and concentration After the lymphoma appears to have resolved more formal and intensive tests are done The intensive tests are repeated each year and shorter interim tests are done about every 6 months Also a specialist periodically monitors patients understanding of HAART and the importance of this therapy
Blood tests Blood is drawn every day during hospitalizations to measure methotrexate levels and to evaluate kidney and liver function and blood counts Blood is also drawn before starting therapy when the lymphoma disappears 6 months after completing treatment and any time it appears that the lymphoma may have recurred to test for Epstein-Barr virus EBV a virus that is almost always present in AIDS-related primary brain lymphoma
Imaging tests Patients undergo magnetic resonance imaging MRI and positron emission tomography PET scans periodically to monitor the effects of treatment on the lymphoma MRI scans are done after the 2nd 4th 6th and 8th treatments then every 2 months for three times every 3 months for six times every 6 months for four times and then every year for 5 years or sooner if there is a concern about the brain PET scans are done after the first cycle after the MRI suggests the lymphoma is gone and then yearly
Lumbar puncture spinal tap This test is done to look for EBV in the cerebrospinal fluid CSF Under local anesthetic a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord and a small amount of fluid is collected through the needle This test is done at the same times as the blood tests for EBV
Eye examinations Patients eyes are examined periodically because brain lymphoma can sometimes spread to the eye and because some people with AIDS-related primary brain lymphoma are at risk of certain eye infections
Detailed Description:
Background Acquired Immunodeficiency Syndrome AIDS-related primary central nervous system lymphoma AR-PCNSL is an Epstein-Barr virus EBV-driven lymphoproliferative process that typically results in death within a few months Essentially all of the cases are immunoblastic cluster of differentiation 20 CD20 tumors and occur once the cluster of differentiation 4 CD4 cells have fallen to below 50 cellsmm3 Highly active antiretroviral therapy HAART can result in immune reconstitution that decreases the risk of AR-PCNSL However a subset of human immunodeficiency virus HIV-infected patients still develops ARPCNSL often because they are unaware that they are HIV infected or they do not take HAART Treatment options for such patients are limited In the non-AIDS setting chemotherapy has become the standard of care for primary central nervous system lymphoma PCNSL and late neurocognitive decline consequent to radiotherapy can be avoided by such approaches In the pre-HAART era AR-PCNSL was generally treated with whole brain radiotherapy however death due to recurrent lymphoma or to other AIDS complications occurred prior to the potential manifestations of late occurring radiation-related neurotoxicity Radiation-sparing approaches have not been studied in AR-PCNSL in the HAART era where advances in antiretroviral therapy have made curative intent chemotherapy feasible for most patients with HIV infection
Objectives The primary objective of this study is to estimate the fraction of patients with AR-PCNSL receiving experimental treatment consisting of HAART combined with rituximab high-dose methotrexate and leucovorin R-HD-MTX who are alive and without recurrent lymphoma or severe cognitive problems at two years
Eligibility HIV-infected age 18 years or older AR-PCSNL that has not previously been treated and be able to give informed consent or have a durable power of attorney who can provide informed consent HIV profile that makes them likely to respond to HAART There are a number of other specific inclusion and exclusion criteria in part to exclude patients who would be unlikely to tolerate the therapy
Design Phase II pilot study investigating R-HD-MTX given with leucovorin rescue and HAART as a treatment for AR-PCNSL Evaluation will include quantitative measurement of lymphocyte subsets quantitative polymerase chain reaction PCR of HIV and EBV viral loads including both blood and cerebrospinal fluid in the case of EBV to assess immune response and anti-viral effects Tumor evaluation with brain magnetic resonance imaging MRI and brain fluoro-2-deoxy-d-glucose positron emission tomography FDG-PET scans will be used for staging and response assessment Longitudinal neuropsychologic testing after complete responses are documented will serve to evaluate neurocognitive parameters post therapy
a separate cohort for additional secondary endpoints
Objectives The primary objective of this study is to estimate the fraction of patients with AR-PCNSL receiving experimental treatment consisting of HAART combined with rituximab high-dose methotrexate and leucovorin R-HD-MTX who are alive and without recurrent lymphoma or severe cognitive problems at two years
Eligibility HIV-infected age 18 years or older AR-PCSNL that has not previously been treated and be able to give informed consent or have a durable power of attorney who can provide informed consent HIV profile that makes them likely to respond to HAART There are a number of other specific inclusion and exclusion criteria in part to exclude patients who would be unlikely to tolerate the therapy
Design Phase II pilot study investigating R-HD-MTX given with leucovorin rescue and HAART as a treatment for AR-PCNSL Evaluation will include quantitative measurement of lymphocyte subsets quantitative polymerase chain reaction PCR of HIV and EBV viral loads including both blood and cerebrospinal fluid in the case of EBV to assess immune response and anti-viral effects Tumor evaluation with brain magnetic resonance imaging MRI and brain fluoro-2-deoxy-d-glucose positron emission tomography FDG-PET scans will be used for staging and response assessment Longitudinal neuropsychologic testing after complete responses are documented will serve to evaluate neurocognitive parameters post therapy
a separate cohort for additional secondary endpoints
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-C-0051 | None | None | None |