AIDS-Related-Primary Central Nervous System Lymphoma Clinical Trial
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
| Verified date | May 2020 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 12 |
| Est. completion date | September 19, 2019 |
| Est. primary completion date | September 18, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 99 Years |
| Eligibility |
- INCLUSION CRITERIA: Positive human immunodeficiency virus (HIV) serology (previous records acceptable) - Diagnosis of Primary Central Nervous System Lymphoma - Confirmed histopathologic diagnosis by National Cancer Institute (NCI) Laboratory of Pathology - If tissue diagnosis is not feasible for any reason, such as undue risk to the patient to acquire tissue diagnosis, the following will be accepted as confirmed Acquired immunodeficiency syndrome-related primary central nervous system lymphoma (AR-PCNSL) diagnosis: - Positive brain fluro-2-deoxy-d-glucose positron emission tomography (FDG-PET) and - Epstein Barr Virus (EBV) detected in the cerebrospinal fluid (CSF) using polymerase chain reaction (PCR) - Age 18 years or greater - Eastern Cooperative Oncology Group (ECOG) performance less than or equal to 0-4 - Ability to understand and willing to provide informed consent - If patient unable to understand informed consent, a previously designated durable power of attorney for healthcare or an individual with legal authority may substitute in this capacity - Assignment of a durable power of attorney for healthcare if not already done EXCLUSION CRITERIA: - Prior therapy for central nervous system (CNS) lymphoma - Steroids not an exclusion - Evidence of lymphoma outside of the central nervous system - Ocular involvement will not exclude - Multidrug resistant HIV not amenable to long-term suppression based on either or both: - Clinical history of poor adherence to multiple antiretroviral drugs deemed sufficient to render effective HIV control unattainable; - HIV mutational analysis (genotyping and/or phenotyping) that reveals high-level resistance to more than 1 class of anti-HIV drugs such that a combination regimen comprised of agents from at least two drug classes can not be devised to suppress HIV long-term. - Refusal to adhere to highly active antiretroviral therapy (HAART) - Concurrent malignancy other than Kaposi sarcoma, resectable squamous cell or basal cell skin cancer, or T1 anal cancer amenable to surgical resection. - Heart failure, Class IV by New York Heart Association criteria - Chronic Liver Disease, Child-Pugh class B or C Pregnancy - Refusal to practice contraception during chemotherapy. - Any condition or set of circumstances that the Principal Investigator or Protocol Chair interprets as creating undue risk to the patient by participating on this study or would make the patient unlikely to comply with the study. |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States,
Goplen AK, Dunlop O, Liestøl K, Lingjaerde OC, Bruun JN, Maehlen J. The impact of primary central nervous system lymphoma in AIDS patients: a population-based autopsy study from Oslo. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Apr 1;14(4):351-4. — View Citation
Levine AM. AIDS-related malignancies: the emerging epidemic. J Natl Cancer Inst. 1993 Sep 1;85(17):1382-97. Review. — View Citation
von Gunten CF, Von Roenn JH. Clinical aspects of human immunodeficiency virus-related lymphoma. Curr Opin Oncol. 1992 Oct;4(5):894-9. Review. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Patients Alive at 2 Years Without Recurrent Brain Lymphoma or Severe Neurocognitive Defects | Recurrent lymphoma as defined by the International Primary Central Nervous System (CNS) Lymphoma Collaborative Group for response assessment of aggressive Non-Hodgkin's Lymphoma (NHL) using fluorodeoxyglucose F 18 (18FDG-PET). Severe cognitive problems are defined as the inability to carry out normal activities with minimal difficulty and not requiring nursing care or hospitalization because of neurological impairment. | 2 years | |
| Secondary | Number of Participants With Serious and Non-serious Adverse Events | Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. | Date treatment consent signed to date off study, approximately 142 months and 11 days. | |
| Secondary | Number of Participants With Response to Treatment After Rituximab, High-Dose Methotrexate (R-HD-MTX) Induction | Response was assessed by the International Workshop Criteria for Non-Hodgkin's Lymphoma. Complete Response is disappearance of all enhancing lesions on magnetic resonance imaging of the brain. Partial Response is a reduction of enhancing tumor volume by more than 50% for at least 4 weeks. Progressive Disease is an increase of tumor volume of more than 25% or occurrence of new lesions. | At the end of 6 cycles or 12 weeks of treatment | |
| Secondary | Estimated Percentage of Participants Overall Survival | Participants that are estimated to be alive or last known to be alive after Rituximab, High-Dose Methotrexate and Leucovorin treatment. | Time from treatment start date until date of death or date last known alive, approximately 60 months | |
| Secondary | Median Mini Mental Status Exam (MMSE) Score in Surviving Participants After Rituximab, High-Dose Methotrexate & Leucovorin ( R-HD-MTX) Treatment | The MMSE is scored out of a maximum of 30 points. A score of >25 is considered normal, with scores <25 indicating different levels of cognitive impairment: mild (21-24) moderate (10-20), and severe (0-10). | up to 2.5 years | |
| Secondary | Change From Baseline in Cluster of Differentiation 4 (CD4) T Cell Count at up to 2.5 Years | An increase in CD4 cells is determined by the number of CD4+ T lymphocytes /µL of peripheral blood. | Baseline and up to 2.5 years |