Granulomatous and Lymphocytic Interstitial Lung DiseasePhase 2NCT02789397
Treatment of Granulomatous and Lymphocytic Interstitial Lung Disease in Patients With Common Variable Immunodeficiency
A Phase 2 study testing Rituximab (RTX) and Azathioprine (AZA) in people with Granulomatous and Lymphocytic Interstitial Lung Disease, run by Medical College of Wisconsin.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Granulomatous and Lymphocytic Interstitial Lung Disease
- What is being tested?
- Rituximab (RTX) and Azathioprine (AZA)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 2 May 2016to 6 Mar 2018
- Phase
- Phase 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
- Age:
- Patients must be 18 years of age or older.
- Diagnosis:
- Diagnosis of CVID in accordance with international criteria which includes: A) Serum immunoglobin G (IgG) at least 2 standard deviations below the age adjusted norm; B) Decreased serum immunoglobin A (IgA) and/or immunoglobin M (IgM); C) Age > 4 years.; D) Abnormal specific antibody production in response to immunization; E) Exclusion of secondary causes of hypogammaglobulinemia.
- Diagnosis of GLILD based on histopathologic abnormalities of lung tissue obtained by open lung biopsy within 12 months of enrollment and confirmed by Pathology Core.
- Performance Level:
Show all 29Show fewer
- Karnofsky Performance Status (KPS) ≥ 50%
- Prior Therapy:
- Patients must have fully recovered from the acute toxic effects of all prior therapy.
- Systemic steroids need to be completed at least 60 days from the time of enrollment.
- Organ Function:
- Adequate Lung Function defined as:
- FVC > 60 % predicted and
- DLco > 35 % predicted
- Adequate Bone Marrow Function defined as:
- Peripheral absolute neutrophil count (ANC) ≥ 750/mm3 and
- Platelet count ≥ 50,000/mm3
- Adequate Hepatic Function as evidenced by:
- Direct Bilirubin < 1.5 x upper limit of normal (ULN) for age
- Serum glutamic pyruvic transaminase (SGPT) (ALT) < 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
- Adequate Renal Function as defined by a normal serum creatinine
- Reproductive Function:
- o Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
- Female patients with infants must agree not to breastfeed their infants while on this study.
- Male and female patients of childbearing potential must agree to use an effective method of contraception approved by the investigator during the study.
- Sexually active females of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device (UD), surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 6 months after the last dose of study therapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 6 months after the last dose of study therapy.
- Regulatory Requirements
- All patients must sign a written informed consent.
- All institutional, FDA, and NIH requirements for human studies must be met.
Who cannot join
- Infection:
- Patients with uncontrolled infection are not eligible.
- Patients with documented serious infection within 3 months of screening or opportunistic infection within 6 months of screening are not eligible.
- Cardiac Function:
- o Patients cannot be diagnosed with New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias, or uncontrolled hypertension.
- Allergies:
Show all 27Show fewer
- o Known hypersensitivity to any of the components of RTX or AZA.
- Current Therapy:
- Systemic immunosuppressive medications including steroids.
- Steroids can be used to prevent or to treat infusion-related RTX symptoms, but this should be used only prior to or immediately after the RTX infusion, and should not be continued beyond 3 days. The use of systemic steroids should be recorded.
- Inhaled steroids are acceptable.
- 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.
- Hepatitis B or Hepatitis C Infection:
- All patients will be screened for Hepatitis B and C by polymerase chain reaction (PCR).
- Hepatitis C positive as determined by PCR.
- Hepatitis B Reactivation: Hepatitis B Reactivation is defined as Hepatitis B carrier patients with one of the following:
- Positive hepatitis B e-antigen (HBe-Ag)
- Quantitative hepatitis B Viral (HBV) DNA Load > 10^5 genomes/ml
- Human Immunodeficiency Virus (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.
About this study
Official title: Clinical Trial to Assess the Efficacy of Rituximab and Azathioprine in the Treatment of Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) in Adult Patients With Common Variable Immunodeficiency (CVID)
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.
Read the detailed description
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:
- Your study infusions
- Physical exams with vital signs
- Blood tests to check your organ function
Every six months (Enrollment, 6, 12 \& 18 months) while receiving study treatment, patients will be asked to complete the following study tests:
- Lung Function testing
- High resolution CT of the chest
- Quality of Life Questionnaire, 6-min walk distance test and Karnofsky performance scale.
- Blood for research - approximately 10 teaspoons of blood will be collected
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:
- Physical exams with vital signs
- Lung Function testing
- High resolution CT of the chest
- Quality of Life Questionnaire, 6-min walk distance test and Karnofsky performance scale.
- Blood for research - approximately 10 teaspoons of blood will be collected
- Being tested
- Rituximab (RTX) and Azathioprine (AZA), Placebos
- Keywords
- Granulomatous and lymphocytic interstitial lung disease (GLIILD), common variable immunodeficiency, Rituximab, Azathioprine, primary immunodeficiency, GLIILD, CVID
- Medical subject headings
- Common Variable Immunodeficiency, Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab (RTX) and Azathioprine (AZA)Drug
Also called Truxima
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).
PlacebosDrug
Also called Saline
IV placebo will be administered on the same schedule as Rituximab and oral placebo will be administered by mouth daily for 18 months.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab (RTX) and Azathioprine (AZA) | Active comparator | 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. Receives: Drug: Rituximab (RTX) and Azathioprine (AZA) |
| Placebo | Placebo comparator | IV placebo will be administered on the same schedule as Rituximab. Oral placebo will be administered by mouth daily for 18 months. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 18 months
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2016 (estimated)
- Study start2 May 2016
- Primary completion6 Mar 2018
- Study completion6 Mar 2018
Why it stopped: No funding for study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Granulomatous and Lymphocytic Interstitial Lung DiseaseStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John M. Routes, Medical College of Wisconsin
- Investigators
- John M Routes, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02789397
- Sponsor's protocol ID
- PRO26723
- Status last verified
- Mar 2020
- First submitted
- 16 May 2016
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zdziarski P, Gamian A. Lymphoid Interstitial Pneumonia in Common Variable Immune Deficiency - Case Report With Disease Monitoring in Various Therapeutic Options: Pleiotropic Effects of Rituximab Regimens. Front Pharmacol. 2019 Jan 18;9:1559. doi: 10.3389/fphar.2018.01559. eCollection 2018.
PubMed 30713498
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial to Assess the Efficacy of Rituximab and Azathioprine in the Treatment of Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) in Adult Patients With Common Variable Immunodeficiency (CVID)
- ClinicalTrials.gov ID
- NCT02789397
- Acronym / sponsor ID
- PRO26723
- Keywords
- Granulomatous and lymphocytic interstitial lung disease (GLIILD), common variable immunodeficiency, Rituximab, Azathioprine, primary immunodeficiency, GLIILD, CVID
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No funding for study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 2 May 2016 (actual)
- Primary completion
- 6 Mar 2018 (actual)
- Study completion
- 6 Mar 2018 (actual)
- First posted
- 3 Jun 2016 (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.
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.
Detailed description
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:
- Your study infusions
- Physical exams with vital signs
- Blood tests to check your organ function
Every six months (Enrollment, 6, 12 \& 18 months) while receiving study treatment, patients will be asked to complete the following study tests:
- Lung Function testing
- High resolution CT of the chest
- Quality of Life Questionnaire, 6-min walk distance test and Karnofsky performance scale.
- Blood for research - approximately 10 teaspoons of blood will be collected
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:
- Physical exams with vital signs
- Lung Function testing
- High resolution CT of the chest
- Quality of Life Questionnaire, 6-min walk distance test and Karnofsky performance scale.
- Blood for research - approximately 10 teaspoons of blood will be collected
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab (RTX) and Azathioprine (AZA) | Active comparator | Drug: Rituximab (RTX) and Azathioprine (AZA)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. |
| Placebo | Placebo comparator | Drug: PlacebosIV placebo will be administered on the same schedule as Rituximab. Oral placebo will be administered by mouth daily for 18 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Patients must be 18 years of age or older.
- Diagnosis of CVID in accordance with international criteria which includes: A) Serum immunoglobin G (IgG) at least 2 standard deviations below the age adjusted norm; B) Decreased serum immunoglobin A (IgA) and/or immunoglobin M (IgM); C) Age > 4 years.; D) Abnormal specific antibody production in response to immunization; E) Exclusion of secondary causes of hypogammaglobulinemia.
- Diagnosis of GLILD based on histopathologic abnormalities of lung tissue obtained by open lung biopsy within 12 months of enrollment and confirmed by Pathology Core.
- Karnofsky Performance Status (KPS) ≥ 50%
- Patients must have fully recovered from the acute toxic effects of all prior therapy.
Key exclusion criteria (27 listed)
- Patients with uncontrolled infection are not eligible.
- Patients with documented serious infection within 3 months of screening or opportunistic infection within 6 months of screening are not eligible.
- o Patients cannot be diagnosed with New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias, or uncontrolled hypertension.
- o Known hypersensitivity to any of the components of RTX or AZA.
- Systemic immunosuppressive medications including steroids.
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 |
|---|---|---|
| Rituximab (RTX) and Azathioprine (AZA)Also: TruximaRituximab 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). | Drug | Rituximab (RTX) and Azathioprine (AZA) |
| PlacebosAlso: SalineIV placebo will be administered on the same schedule as Rituximab and oral placebo will be administered by mouth daily for 18 months. | Drug | Placebo |
Primary outcome
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.
Time frame: Baseline and 18 months
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.
13 secondary outcomes
The effect of treatment with RTX/AZA relative to placebo on the changes over time in high-resolution CT scans of the chest.
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.
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.
Time frame: 24 months
Changes in FVC and HRCT of the chest (maintained for 6 months after completion of therapy in both randomized groups)
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.
Time frame: 24 months
Changes in quality of life in the two randomized groups of patients as measured by SGRQ total score.
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).
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.
Time frame: Baseline, six months, 12 months, 18 months and 24 months
Dysregulated molecular pathway determined by performing whole transcriptome sequencing.
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.
Time frame: 24 Months
Peripheral blood biomarkers as indicators of GLILD disease activity.
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.
Time frame: 24 Months
Prevalence and abundance of bacterial, fungal and viral sequences.
Time frame: 24 Months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Derived from this study: PubMed 30713498Zdziarski P, Gamian A. Lymphoid Interstitial Pneumonia in Common Variable Immune Deficiency - Case Report With Disease Monitoring in Various Therapeutic Options: Pleiotropic Effects of Rituximab Regimens. Front Pharmacol. 2019 Jan 18;9:1559. doi: 10.3389/fphar.2018.01559. eCollection 2018.
- Individual participant dataSharing planned: No
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.
John M Routes, MD principal investigator
Medical College of Wisconsin
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab (RTX) and Azathioprine (AZA) in people with Granulomatous and Lymphocytic Interstitial Lung Disease, run by Medical College of Wisconsin.
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 29 inclusion and 27 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: withdrawn, as of the sponsor's last update on 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 was withdrawn before enrolling participants, so there are no results.
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?
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. (time frame: Baseline and 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02789397, which also lists 1 linked publication.
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 10 Mar 2020.