Treatment of Granulomatous and Lymphocytic Interstitial Lung Disease in Patients With Common Variable Immunodeficiency

• Status: Withdrawn
• Trial end date: 2018-03-06
• Target enrollment: 0
• Participant gender: All

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. The researchers will also assess if the drugs improved quality of life.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical College of Wisconsin
• Treatments: Azathioprine; Rituximab

Criteria

INCLUSION CRITERIA:

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:

• 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.

EXCLUSION CRITERIA:

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:

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.