Rituximab for Pulmonary Sarcoidosis

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Sarcoidosis is a inflammatory disease affecting many parts of the body, especially the lungs. While most patients do well, there is a group of patients who require continuous doses of prednisone or other drugs. The current study will determine the role of Rituximab as new agent for patients with refractory disease.

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

Details

• Lead Sponsor: University of Cincinnati
• Collaborator: University of Chicago
• Treatments: Rituximab

Criteria

Inclusion Criteria:

1. Men and women > 18 years of age.

2. Sarcoidosis diagnosed at least 1 year prior to screening.

3. Histological proven sarcoidosis prior to screening.

4. Have a diagnosis of severe sarcoidosis with evidence of parenchymal disease on chest radiograph (Stage III) or abnormal PFT, with histologic and there should be an evidence of sarcoid (involvement by biopsy ( pulmonary or extrapulmonary)) . Subjects with concurrent extrapulmonary sarcoidosis particularly skin and eye involvement are encouraged to be enrolled. Patients with neurologic sarcoidosis will be excluded.

5. Have FVC > 40 and < 80% of predicted.

6. Have an ATS dyspnea score of > Grade 1.

7. Have been receiving pre-study treatment that includes at least 10 mg/day of prednisone or equivalent dose of corticosteroids as a single agent, and/or methotrexate, or hydroxychloroquine for at least the 3-month period prior to screening. Subjects must be on a stable dose of these meds for > 4 weeks before starting the study medication.

8. Adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) must be used for the duration of the study and should continue such precautions for 6 12 months after receiving the last study infusion.

9. Are considered eligible based on TB screening.

10. Are capable of reading and understanding subject assessment forms and providing written informed consent.

11. Are willing and able to adhere to the study visit schedule and other protocol-specified procedures.

Exclusion Criteria:

Laboratory Exclusion Criteria

1. Hemoglobin: < 8.5 gm/dL

2. Platelets: < 100,000/mm

3. Serum Creatinine: > 1.4

4. Neutrophils: < 1.5 x mm3

5. IgG: < 5.6 mg/dl and IgM: < .55 mg/dl

6. AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.

7. Positive Hepatitis B or C serology (Hep B surface antigen and Hep C antibody)

General Safety Exclusion Criteria

1. Previous Treatment with Rituximab (MabThera® / Rituxan®)

2. Previous administration of a treatment with any other therapeutic agent targeted at depleting B cells within 12 months prior to screening.

3. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)

4. Current treatment with TNF inhibitors, cyclosporine, tacrolimus or leflunomide.

5. Treatment with TNF inhibitors within (8 weeks prior to screening), cyclosporine or tacrolimus ( 4 weeks prior to screening) or leflunomide ( 8 weeks prior to screening, or 25 days after cholestyramine washout).

6. Previous treatment within 6 months with IVIg.

7. Parenteral corticosteroids within 4 weeks prior to screening visit.

8. Receipt of live virus or bacterial vaccinations within the 4 weeks before the first dose of the study agent or are expected to receive any live virus or bacterial vaccinations during the trial or up to 3 months after the last dose of the study agent

9. History of severe allergic or anaphylactic reactions associated with the administration of humanized or murine monoclonal antibodies

10. History of New York Heart Association (NYHA) Class III or IV congestive heart failure(CHF)

11. History of severe right-sided heart failure or cor pulmonale

12. Known active bacterial, viral, fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 2 months of screening or oral antibiotics within 2 weeks prior to screening

13. History of recurrent significant infection or history of recurrent bacterial infections

14. History of opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis and aspergilloma, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening

15. History of known infection with human immunodeficiency virus (HIV)

16. Considered ineligible according to the USA-specific TB screening

17. Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation

18. Current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases (with the exception of sarcoidosis).

19. Have normal pulmonary function

20. Have any clinical evidence of intracranial lesions.

21. Have an abnormal neurological examination during baseline assessment

22. Have neurosarcoidosis

23. Have a known history of demyelinating disease such as multiple sclerosis or optic neuritis.

24. Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

25. Have poor tolerability of intravenous infusion or lack of adequate venous access for required blood sampling.

26. History of transplanted organ (with the exception of a corneal transplant > 3 months prior to screening.

27. History of substance abuse or dependency, drug or alcohol within 3 years of screening

28. History of primary or secondary immunodeficiency

29. History of psychiatric disorder that would interfere with normal participation in this protocol

30. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.

31. Inability to comply with study and follow-up procedures

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