Anakinra in Previously Untreated Chronic Lymphocytic Leukemia Patients

• Status: Not yet recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase I trial of the IL-1 receptor antagonist anakinra in chronic lymphocytic leukemia patients who are predicted to eventually require first-line therapy based on conventional clinical criteria. Three groups of 4 patients will be injected subcutaneously with either 100 mg daily or 100 mg twice daily or 200 mg twice daily for 7 cycles of 4 weeks each to determine the dose-limiting toxicity of anakinra in this population. Clinical responses will be determined by conventional IWCLL criteria. It is hoped anakinra will prevent disease progression with little toxicity. The study is anticipated to be completed within a year.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dr. David Spaner
• Collaborators: Sobi; Swedish Orphan Biovitrum
• Treatments: Interleukin 1 Receptor Antagonist Protein

Criteria

Inclusion Criteria:

1. Diagnosis of CLL meeting published diagnostic criteria: monoclonal B cells (either kappa or lambda light chain restricted) that are clonally co-expressing at least 1 B-cell marker (CD19 or CD20) and CD5 with prolymphocytes comprising no more than 55% of blood lymphocytes.

2. Unmutated IGHV status or Rai stage 2-4 or Rai stage 0-1 with blood lymphocytes greater than 30 x 106 cells/ml or IgG less than 8 g/L.

3. Not currently treated with other agents for CLL.

4. Serum bilirubin, and alanine transferase less than or equal to twice the upper limit of normal.

5. Platelets > or equal to 75x109/L. ANC > or equal to.75x109/L. Hemoglobin > or equal to 65 g/L

6. Age>18 years old

7. ECOG<2

Exclusion Criteria:

1. Patients with inadequate bone marrow reserve at baseline visit as demonstrated by at least one of the following: a. ANC<.75x109/L b. platelets <75x109/L without the assistance of growth factors, thrombopoietic factors, or platelet transfusions. C. hemoglobin <65 g/L despite transfusions.

2. Patients who have or have had progressive multifocal leukoencephalopathy (PML).

3. Patients with clinically significant bacterial, fungal, parasitic or viral infection, which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.

4. Patients with known active hepatitis A, B, C or who are HIV-positive or who are at risk for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Prior test results obtained as part of standard of care that confirm a subject is immune and not at risk for reactivation (ie, hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of eligibility and tests do not need to be repeated. Subjects with prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.

5. Primary immunodeficiency such as X-linked agammaglobulinemia or common variable immunodeficiency.

6. Patients with active and inactive ('latent') tuberculosis infection or suspicion of active tuberculosis. If no suspicion of active tuberculosis, testing is not required.

7. Involvement of the central nervous system by lymphoma or leukemia.

8. Richter's transformation or prolymphocytic leukemia.

9. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.

10. Use of glucocorticoids above the equivalent of 10 mg of prednisone daily within 4 weeks prior to treatment with anakinra. Patients cannot previously have taken drugs or antibodies normally used to treat CLL (eg. chlorambucil, fludarabine, cyclophosphamide, bendamustine, rituximab, ofatumumab, ibrutinib, venetoclax).

11. Major surgery within 4 weeks prior to treatment.

12. Patients with a history of malignancy in the past 3 years except for treated, early-stage squamous or basal cell carcinoma, carcinoma-in-situ of the cervix, or low-risk prostate cancer after curative therapy.

13. History or current diagnosis of uncontrolled or significant cardiac disease, including any of the following: a. myocardial infarction within last 6 months. b. uncontrolled congestive heart failure. c. unstable angina within last 6 months. d. exertional angina. e. clinically significant (symptomatic) cardiac arrhythmias (eg. bradyarrhythmias, sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemarker).

14. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

15. Presence of severe renal function impairment (estimated creatinine clearance <30 mL/min/1.73m2).

16. Patients with mild, moderate, or severe hepatic impairment or inadequate liver function defined by any of direct bilirubin, alanine amino transferase (ALT), or aspartate aminotransferase (AST)>2.5 x upper limit of normal (ULN). Patients with Child-Pugh score >5 are also excluded.

17. Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of screening or 5 half-lives (whichever is longer) prior to the first dose of investigational product.

18. Significant concurrent, uncontrolled medical condition which, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.

19. Subjects who are unable to comprehend or are unwilling to sign an informed consent form (ICF).