Chronic Lymphocytic Leukemia Clinical Trial

A Phase I/II Study of Intratumoral Injection of SD-101

Summary

This phase 1-2 trial studies the side effects and best dose of ipilimumab in combination with toll-like receptor 9 (TLR9) agonist SD-101 and radiation therapy in treating patients with recurrent low-grade B-cell lymphoma.

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Full Description

Monoclonal antibodies, such as ipilimumab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as TLR9 agonist SD-101, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving ipilimumab in combination with TLR9 agonist SD-101 and radiation therapy may be a better treatment for B-cell lymphoma.

Study objectives are dose-limiting toxicity (DLT) and the treatment assessments tumor response and time-to-progression. Cohort 1 dose level is 10 mg ipilimumab, subsequent cohort is 5 or 25 mg ipilimumab.

If 2 out of 6 patients experience a DLT in the first cohort (10 mg ipilimumab), the dose will be de-escalated to 5 mg ("Cohort -1").
If 2 out of 6 patients experience a DLT at the 5 mg dose level, then the study will be stopped.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria

Biopsy-confirmed low-grade B-cell lymphoma, specifically, follicular grade 1 or 2, or 3A marginal zone or small lymphocytic lymphoma; patients must have relapsed from or are refractory to prior therapy
Patients must have at least one site of disease that is accessible for intratumoral injection of SD-101 and of ipilimumab (diameter ≥ 10mm), percutaneously
Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the study
Patients must have measurable disease other than the injection site or biopsy site
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 [corresponds to Karnofsky Performance Status (KPS) of ≥ 70]
White blood cell count (WBC) ≥ 2000/µL (2 x 10^9/L)
Absolute neutrophil count (ANC) ≥ 1000/µL (0.5 x 10^9/L)
Platelets ≥ 75 x 10^3/µL (75 x 10^9/L)
Hemoglobin ≥ 8 g/dL (may be transfused)
Creatinine ≤ 2.0 x upper limit of normal (ULN)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN for subjects without liver metastasis; ≤ 5 times for liver metastases
Bilirubin ≤ 2.0 x ULN (except for subjects with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
No active or chronic infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
Must be at least 4 weeks since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, and 8 weeks since any monoclonal antibodies or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
Patients of reproductive potential must agree to use an effective (> 90% reliability) form of contraception during the study and for 6 months following the last study drug administration
Women of reproductive potential must have negative urine pregnancy test
Life expectancy greater than 4 months
Able to comply with the treatment schedule
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Pre-existing autoimmune or antibody mediated disease including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, Addison's disease, but excluding the presence of auto-antibodies without clinical autoimmune disease
History of inflammatory bowel disease (eg, Crohn's disease or ulcerative colitis), celiac disease, or other chronic gastrointestinal conditions associated with diarrhea, or current acute colitis of any origin
Any history of diverticulitis, or evidence of diverticulitis at baseline, including evidence limited to computed tomography (CT) scan only (note diverticulosis is not an exclusion criterion)
Severe psoriasis
Active thyroiditis
History of uveitis
Known history of HIV; patients with Acquired Immunodeficiency Syndrome (AIDS) are excluded
Patients with active infection or with a fever > 38.5 degrees C within 3 days prior to the first scheduled treatment
Central nervous system (CNS) lymphoma
Prior malignancy (active within 5 years of screening) except basal cell or completely excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell carcinoma of the cervix
History of allergic reactions attributed to compounds of similar composition to SD-101 or ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] antibodies)
Current anticoagulant therapy (EXCEPTION acetylsalicylic acid ≤ 325 mg per day allowed)
Treatment with an immunosuppressive regimen of corticosteroids or other immunosuppressive medication (eg, methotrexate, rapamycin) within 30 days of study treatment; note patients with adrenal insufficiency may take up to 5 mg of prednisone or equivalent daily; topical and inhaled corticosteroids in standard doses are allowed
Significant cardiovascular disease [ie, New York Heart Association (NYHA) class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias]
Pregnant or lactating
Any other medical history, including laboratory results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results.

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 1

Estimated Enrollment:

9

Study ID:

NCT02254772

Recruitment Status:

Completed

Sponsor:

Robert Lowsky

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There is 1 Location for this study

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Stanford University Hospitals and Clinics
Stanford California, 94305, United States

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Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 1

Estimated Enrollment:

9

Study ID:

NCT02254772

Recruitment Status:

Completed

Sponsor:


Robert Lowsky

How clear is this clinincal trial information?

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