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NCT00267865

Chemotherapy and HAART to Treat AIDS-related Primary Brain Lymphoma

Completed Phase 2 Results posted Last updated 1 June 2020
What this trial tests

Phase 2 trial testing Methotrexate in AIDS-Related-Primary Central Nervous System Lymphoma in 12 participants. Completed in 19 September 2019.

Timeline
14 September 2006
Primary endpoint
18 September 2019
19 September 2019

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment12
Start date14 September 2006
Primary completion18 September 2019
Estimated completion19 September 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 99, any sex, with AIDS-Related-Primary Central Nervous System Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients Alive at 2 Years Without Recurrent Brain Lymphoma or Severe Neurocognitive Defects Primary · 2 years

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.

GroupValue95% CI
Rituximab, High-Dose Methotrexate & Leucovorin Treatment8
Number of Participants With Serious and Non-serious Adverse Events Secondary · Date treatment consent signed to date off study, approximately 142 months and 11 days.

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

GroupValue95% CI
Rituximab, High-Dose Methotrexate & Leucovorin Treatment11
Number of Participants With Response to Treatment After Rituximab, High-Dose Methotrexate (R-HD-MTX) Induction Secondary · At the end of 6 cycles or 12 weeks of treatment

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.

Complete Response
GroupValue95% CI
Rituximab, High-Dose Methotrexate & Leucovorin Treatment5
Partial Response
GroupValue95% CI
Rituximab, High-Dose Methotrexate & Leucovorin Treatment4
Progressive Disease
GroupValue95% CI
Rituximab, High-Dose Methotrexate & Leucovorin Treatment1
Estimated Percentage of Participants Overall Survival Secondary · Time from treatment start date until date of death or date last known alive, approximately 60 months

Participants that are estimated to be alive or last known to be alive after Rituximab, High-Dose Methotrexate and Leucovorin treatment.

GroupValue95% CI
Rituximab, High-Dose Methotrexate & Leucovorin Treatment6632 – 86
Median Mini Mental Status Exam (MMSE) Score in Surviving Participants After Rituximab, High-Dose Methotrexate & Leucovorin ( R-HD-MTX) Treatment Secondary · up to 2.5 years

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).

GroupValue95% CI
Rituximab, High-Dose Methotrexate & Leucovorin Treatment2827 – 30
Change From Baseline in Cluster of Differentiation 4 (CD4) T Cell Count at up to 2.5 Years Secondary · Baseline and up to 2.5 years

An increase in CD4 cells is determined by the number of CD4+ T lymphocytes /µL of peripheral blood.

GroupValue95% CI
Rituximab, High-Dose Methotrexate & Leucovorin Treatment35-54 – 369

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 142 months and 11 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rituximab, High-Dose Methotrexate & Leucovorin Treatment
Serious: 3/12 (25%)
Deaths: 3/12

Serious adverse events (5 terms)

ReactionSystemRituximab, High-Dose Metho…
Death not associated with CTCAE term::Death NOSGeneral disorders
Death not associated with CTCAE term::Disease progression NOSGeneral disorders
Hemorrhage, GI::Upper GI NOSGastrointestinal disorders
Pulmonary/Upper Respiratory - Other (Specify, Patient intubated)Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other (Specify, Pulmonary embolism)Respiratory, thoracic and mediastinal disorders
Other adverse events (106 terms — click to expand)

ReactionSystemRituximab, High-Dose Metho…
AST, SGOT(serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders
Leukocytes (total WBC)Blood and lymphatic system disorders
Albumin, serum-low (hypoalbuminemia)Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)Metabolism and nutrition disorders
HemoglobinBlood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)Blood and lymphatic system disorders
ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)Metabolism and nutrition disorders
PlateletsBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
Potassium, serum-low (hypokalemia)Metabolism and nutrition disorders
Alkaline phosphataseMetabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)Metabolism and nutrition disorders
CD4 countBlood and lymphatic system disorders
DiarrheaGastrointestinal disorders
Infection - Other (Specify, HSV)Infections and infestations
Sodium, serum-high (hypernatremia)Metabolism and nutrition disorders
Calcium, serum-high (hypercalcemia)Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)Metabolism and nutrition disorders
CreatinineMetabolism and nutrition disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)General disorders
Memory impairmentNervous system disorders
Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders
Cognitive disturbanceNervous system disorders
ConfusionNervous system disorders
Potassium, serum-high (hyperkalemia)Metabolism and nutrition disorders
ProteinuriaMetabolism and nutrition disorders
Weight gainGeneral disorders
Ataxia (incoordination)Nervous system disorders
Bilirubin (hyperbilirubinemia)Metabolism and nutrition disorders
CPK (creatine phosphokinase)Metabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
Fatigue (asthenia, lethargy, malaise)General disorders
Glucose, serum-low (hypoglycemia)Metabolism and nutrition disorders
HypertensionCardiac disorders
HypotensionCardiac disorders
Infection with normal ANC or Grade 1 or 2 neutrophils::Urinary tract NOSInfections and infestations
Magnesium, serum-high (hypermagnesemia)Metabolism and nutrition disorders
NauseaGastrointestinal disorders

Most-reported serious reactions: Death not associated with CTCAE term::Death NOS, Death not associated with CTCAE term::Disease progression NOS, Hemorrhage, GI::Upper GI NOS, Pulmonary/Upper Respiratory - Other (Specify, Patient intubated), Pulmonary/Upper Respiratory - Other (Specify, Pulmonary embolism).

Data from ClinicalTrials.gov NCT00267865 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Treatment of HIV-associated primary CNS lymphoma with antiretroviral therapy, rituximab, and high-dose methotrexate.
    Lurain K, Uldrick TS, Ramaswami R, Polizzotto MN, et al · · 2020 · cited 24× · PMID 32609814 · DOI 10.1182/blood.2020006048
  2. Evolving Paradigms in HIV Malignancies: Review of Ongoing Clinical Trials.
    Bender Ignacio RA, Lin LL, Rajdev L, Chiao E. · · 2018 · cited 9× · PMID 30099376 · DOI 10.6004/jnccn.2018.7064
  3. Paradoxical central nervous system immune reconstitution syndrome in acquired immunodeficiency syndrome-related primary central nervous system lymphoma.
    Kranick SM, Goncalves PH, Stetler-Stevenson M, Aleman K, et al · · 2015 · cited 2× · PMID 25304612 · DOI 10.3324/haematol.2014.114736

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00267865.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing