A Phase 2 interventional study of Rituximab (RTX) and Azathioprine (AZA) and Placebos in Granulomatous and Lymphocytic Interstitial Lung Disease, sponsored by Medical College of Wisconsin. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-03-10.
Sponsored by Medical College of Wisconsin · Phase 2, Interventional, and Treatment
This phase II study will assess the effect of a treatment combination of Rituximab and azathioprine in patients with Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) compared to placebo, based on change in lung function at 18 months compared to baseline. The researchers will also assess if the drugs improved quality of life.
BACKGROUND Common Variable Immunodeficiency (CVID) is one of the most clinically important primary immunodeficiencies due to its frequency, serious complications, and long-term costs of therapy. A form of lung disease known as granulomatous and lymphocytic interstitial lung disease (GLILD) occurs in 10-15% of patients with CVID. The causes of GLILD are unknown; no long-term study has defined the natural course of GLILD; and no clinical trials have been done to define the best possible treatment for this condition. As a result, currently there is no proven standard of care for the treatment of GLILD.
The best treatment for individuals with GLILD is not currently known. Some doctors believe that GLILD does not always continue to get worse and patients should only be treated unless this happens. Other doctors believe GLILD is always progressive and should be treated early to prevent more problems later.
There is compelling evidence to support that treatment using rituximab (RTX) in conjunction with azathioprine (AZA), may improve the lung function and abnormalities seen on high resolution CT (HRCT) scans of the chest.
STUDY GROUPS Patients in this study will either receive a placebo or a combination of Rituximab and azathioprine. These drugs are approved by the US Food and Drug Administration for other conditions, but not yet for this disease.
Because no one knows which of the treatments is best, patients will be "randomized" into one of the two study groups. Randomization means that you are put into a group by chance.
TREATMENT Eligible patients will be randomized to receive either 18 months of Rituximab and Azathioprine (20 patients) or placebo (20 patients). Rituximab will be administered intravenously (IV) weekly for four consecutive weeks at enrollment and months 6 and 12. IV placebo will be administered on the same schedule as Rituximab. Azathioprine or oral placebo will be administered by mouth daily for 18 months.
SUMMARY OF STUDY PROCEDURES
-Month 1, 6, 12
Patients will be required to travel to a study site weekly for four consecutive weeks at enrollment and at 6 and 12 months to receive study infusions. At each of these visits, patients will be given:
Every six months (Enrollment, 6, 12 \& 18 months) while receiving study treatment, patients will be asked to complete the following study tests:
Monthly Labs Following the first month of study treatment, patients will be required to visit their local clinic/hospital for a blood draw to monitor their lab values twice monthly for the second and third months of treatment, then monthly.
Final Study Visit
The final study visit will take place at Month 24 after start of study treatment. Patients will also have the following tests done:
54 studies on the registry are indexed under Common Variable Immunodeficiency; 13 are open to participants now.
Browse Common Variable Immunodeficiency studies →Medical College of Wisconsin is the lead sponsor of 548 studies on the registry; 122 are open to participants now.
Of its 75 completed or terminated interventional studies of FDA-regulated products, 57 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Age:
Diagnosis:
Performance Level:
Prior Therapy:
Organ Function:
Adequate Lung Function defined as:
Adequate Bone Marrow Function defined as:
Adequate Hepatic Function as evidenced by:
Reproductive Function:
o Female patients of must have a negative urine or serum pregnancy test confirmed prior to enrollment.
Regulatory Requirements
EXCLUSION CRITERIA:
Infection:
Cardiac Function:
o Patients cannot be diagnosed with (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias, or uncontrolled hypertension.
Allergies:
o Known to any of the components of RTX or AZA.
Current Therapy:
Previous Therapy:
o Previous treatment with RTX or AZA for GLILD.
Pregnant Females:
o Pregnant females will not be allowed to participate in this study.
Hepatic Disease:
o Known cirrhosis and/or portal hypertension.
or Infection:
Hepatitis B Reactivation: Hepatitis B Reactivation is defined as Hepatitis B carrier patients with one of the following:
(HIV) 1 Positive:
o HIV 1 infection will be determined by PCR.
Homozygous Mutations:
o Patients with homozygous mutations of thiopurine methyltransferase (TPMT) will be excluded from the study.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Rituximab 375 mg/m2/dose IV over 4 hours first dose, IV over 2-3 hours each subsequent dose weekly for 4 weeks at enrollment and again at months 6 and 12. Azathioprine: Starting dose of azathioprine will be 50 mg and increased in 25 mg increments to a maximum dose of 150 mg or 2 mg/k/day (whichever is lowest) as tolerated. Azathioprine will be administered by mouth daily for 18 months.
Drug: Rituximab (RTX) and Azathioprine (AZA)
IV placebo will be administered on the same schedule as Rituximab. Oral placebo will be administered by mouth daily for 18 months.
Drug: Placebos
Drug pages: Rituximab · Azathioprine
Rituximab 375 mg/m2/dose IV over 4 hours first dose, IV over 2-3 hours each subsequent dose weekly for 4 weeks at enrollment and again at months 6 and 12 for the active comparator arm Rituximab (RTX) and Azathioprine (AZA).
Also known as: Truxima
IV placebo will be administered on the same schedule as Rituximab and oral placebo will be administered by mouth daily for 18 months.
Also known as: Saline
The effect of treatment with RTX/AZA in patients with GLILD compared to placebo, based on change in forced vital capacity (FVC) at 18 months compared to baseline.
Pulmonary Function Tests (PFTs) will be performed to measure lung volumes and airflow for evidence of restrictive and obstructive lung disease. PFTs are used to measure lung volumes and airflow for evidence of restrictive and obstructive lung disease. Measurements will be obtained by standard techniques following guidelines outlined by the American Thoracic Society. Spirometry, during screening, needs to be done pre- and post-bronchodilator. All subsequent spirometry is done post-bronchodilator. Diffusion capacity for carbon monoxide is always done post-bronchodilator. Spirometry will be performed to access the forced expiratory volume (FEV1) and forced vital capacity (FVC). Carbon monoxide diffusion capacity will be performed to assess gas exchange.
Time frame: Baseline and 18 months
The effect of treatment with RTX/AZA relative to placebo on the changes over time in high-resolution CT scans of the chest.
Non-contrast, low dose HRCT scans of the chest will be performed at the intervals and analyzed. Studies will be performed on high-end scanners (64 or above detector rows) capable of producing thin section (1-1.25mm) lung algorithm scans.
Time frame: Baseline, six months, 12 months, 18 months, 24 months
Correlate changes in pulmonary function (FVC, FEV1, DLco) with extent of pulmonary fibrosis obtained on open lung biopsy.
Pulmonary Function Tests (PFTs) will measure forced vital capacity, forced expiratory volume in one second, diffusing capacity of the lungs for carbon monoxide (DLCO) (e.g., DLco will be measured by the single-breath technique using a 10-second breath hold). Histopathologic abnormalities of lung tissue will be determined by open lung biopsy.
Time frame: 24 months
Correlate changes in pulmonary function (FVC, FEV1, DLco) with high-resolution CT scan scores over time in the two randomized groups of patients.
Pulmonary Function Tests (PFTs) will measure forced vital capacity, forced expiratory volume in one second, diffusing capacity of the lungs for carbon monoxide (DLCO) (e.g., DLco will be measured by the single-breath technique using a 10-second breath hold). These will be compared with high-resolution CT scan scores.
Time frame: 24 months
Changes in FVC and HRCT of the chest (maintained for 6 months after completion of therapy in both randomized groups)
Pulmonary Function Tests (PFTs) will measure forced vital capacity, forced expiratory volume in one second, diffusing capacity of the lungs for carbon monoxide (DLCO) (e.g., DLco will be measured by the single-breath technique using a 10-second breath hold). High-resolution CT scans will be performed.
Time frame: Baseline, six months, 12 months, 18 months and 24 months
Incidence of lymphoma in patients treated with RTX/AZA or placebo over the time of enrollment in the study.
Patients will be monitored with physical examinations, laboratory tests (CBC, auto diff, ALT, bilirubin, serum creatinine, platelets, comprehensive lymphocyte phenotype and cell sort).
Time frame: 24 months
Changes in quality of life in the two randomized groups of patients as measured by SGRQ total score.
Quality of life will be measured by the St. George's Respiratory Questionnaire (SGRQ), a pulmonary disease specific questionnaire measuring self-reported dyspnea symptoms and their relationship to activities of daily living and psychological functioning.
Time frame: Baseline, six months, 12 months, 18 months and 24 months
Changes in quality of life in the two randomized groups of patients as measured by Karnofsky Performance Status Scale (KPS).
Karnofsky Performance Status Scale (KPS) will be performed at baseline, six months, 12 months, 18 months and 24 months.
Time frame: Baseline, six months, 12 months, 18 months and 24 months
Changes in quality of life in the two randomized groups of patients as measured by 6-minute Walking Test.
The 6-minute Walking Test will performed at baseline, six months, 12 months, 18 months and 24 months.
Time frame: Baseline, six months, 12 months, 18 months and 24 months
Dysregulated molecular pathway determined by performing whole transcriptome sequencing.
This will be done by performing whole transcriptome sequencing on GLILD, idiopathic pulmonary fibrosis (IPD), sarcoidosis and normal lung tissue.
Time frame: 24 Months
Lung transcriptome predicts response to RTX/AZA therapy (performing whole transcriptome sequencing on GLILD, IPD, sarcoidosis and normal lung tissue) and confirm that lung transcriptome predicts response to RTX/AZA therapy.
This will be done by performing whole transcriptome sequencing on GLILD, IPD, sarcoidosis and normal lung tissue.
Time frame: 24 Months
Peripheral blood biomarkers as indicators of GLILD disease activity.
The research team will examine blood specimens and evaluate Human Leukocyte Antigen - DR isotype (HLA-DR) negative and positive T cells.
Time frame: 24 Months
Presence of bacterial (16S rRNA), fungal (Internal Transcribed Spacer region/ITS) and viral sequences (unbiased high-throughput sequencing) in the lungs of GLILD patients.
This will be done by screening lung biopsies from patients with GLILD, idiopathic pulmonary fibrosis, pulmonary sarcoidosis, or no known pulmonary disease.
Time frame: 24 Months
Prevalence and abundance of bacterial, fungal and viral sequences.
This will be measured with quantitative PCR analysis of lung tissues obtained from patients with GLILD, idiopathic pulmonary fibrosis, pulmonary sarcoidosis or no known lung disease.
Time frame: 24 Months
No study locations are listed for this record.
Plan to share: No
This study is withdrawn, as verified in Mar 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Rituximab · Azathioprine
Common Variable Immunodeficiency →
Medical College of Wisconsin →