Anakinra in Previously Untreated Chronic Lymphocytic Leukemia Patients

NCT04691765 | Unknown Phase 1 DMC

• 1 other identifier: Anakinra
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL; Chronic Lymphocytic Leukemia; Anakinra; type 1 interferon; IFN; dose-limiting toxicity; Kineret

Outcome Measures

Primary Outcomes (1)

• Safety and dose limiting toxicities of anakinra in CLL patients

  The primary endpoints relate to safety and tolerability of anakinra in this patient, including numbers of patients with treatment-related adverse events (AEs) as assessed by CTCAE v4.0

  1 year

Secondary Outcomes (1)

• Efficacy of anakinra in CLL patients

  1 year

Study Arms (3)

100 mg SC

EXPERIMENTAL

100 mg of Kineret (anakinra) will be administered sub-subcutaneously once a day for 28 days (1 cycle) with a maximum of 7 cycles (28 weeks of treatment)

Drug: Kineret

100 mg SC BID

EXPERIMENTAL

100 mg of Kineret (anakinra) will be administered sub-subcutaneously twice a day for 28 days (1 cycle) with a maximum of 7 cycles (28 weeks of treatment)

Drug: Kineret

200 mg SC BID

EXPERIMENTAL

200 mg of Kineret (anakinra) will be administered sub-subcutaneously twice a day for 28 days (1 cycle) with a maximum of 7 cycles (28 weeks of treatment)

Drug: Kineret

Interventions

Kineret DRUG

escalating doses of drug will be administered to 3 groups of 4 patients for 7 months

Also known as: Anakinra

100 mg SC; 100 mg SC BID; 200 mg SC BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Not currently treated with other agents for CLL.
• Serum bilirubin, and alanine transferase less than or equal to twice the upper limit of normal.
• Platelets \> or equal to 75x109/L. ANC \> or equal to.75x109/L. Hemoglobin \> or equal to 65 g/L
• Age\>18 years old
• ECOG\<2

You may not qualify if:

• 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.
• Patients who have or have had progressive multifocal leukoencephalopathy (PML).
• 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.
• 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.
• Primary immunodeficiency such as X-linked agammaglobulinemia or common variable immunodeficiency.
• Patients with active and inactive ('latent') tuberculosis infection or suspicion of active tuberculosis. If no suspicion of active tuberculosis, testing is not required.
• Involvement of the central nervous system by lymphoma or leukemia.
• Richter's transformation or prolymphocytic leukemia.
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
• 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).
• Major surgery within 4 weeks prior to treatment.
• 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.
• 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).
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Presence of severe renal function impairment (estimated creatinine clearance \<30 mL/min/1.73m2).

Sponsors & Collaborators

• Dr. David Spaner: lead
• Swedish Orphan Biovitrum: collaborator

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• David Spaner, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Gallagher, BSc

CONTACT

416-480-6100; jennifer.gallagher@sunnybrook.ca

Geetha Yogendran, BSc

CONTACT

416-480-6100; geetha.yogendran@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Haematologist, Senior Scientist

Model Details: The trial will involve 12 patients in a standard dose escalation design. The first cohort of 4 patients will start at 100 mg SC daily, the dose approved for rheumatoid arthritis. If no dose limiting toxicities are experienced by these patients during the first cycle of treatment, then the next cohort of up to 4 patients will be treated at 100 mg SC twice daily (BID). The third cohort of up to 4 patients will be treated at 200 mg BID SC daily, to approximate doses used to treat inflammopathies such as Cryopyrin-Associated Periodic Syndromes.

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 31, 2020
• Study Start: May 1, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: March 19, 2021

Record last verified: 2020-12