Ruxolitinib Combined With Ibrutinib in Chronic Lymphocytic Leukemia Patients

NCT02912754 | Unknown Phase 1 DMC

• 1 other identifier: CINC424XCA05T
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This study involves adding the kinase inhibitor Ruxolitinib to Ibrutinib to treat Chronic Lymphocytic Leukemia (CLL).

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD) of ruxolitinib in combination with Ibrutinib.

  identify the MTD of ruxolitinib with ibrutinib

  2 years

Secondary Outcomes (1)

• ability of Ruxolitinib to increase the depth of response to Ibrutinib

  2 years

Other Outcomes (1)

• effect of Ruxolitinib on levels of plasma cytokines and chemokines

  3 years

Study Arms (2)

Ibrutinib plus Ruxolitinib

EXPERIMENTAL

Patients taking ibrutinib for relapsed CLL will add ruxolitinib twice per day at the dose identified in a preliminary phase I trial for 7 cycles (3 weeks on/2 weeks off).

Drug: ruxolitinib; Drug: ibrutinib

Ibrutinib alone

NO INTERVENTION

Patients will continue to take Ibrutinib for the equivalent period of time.

Interventions

ruxolitinib DRUG

ruxolitinib will be added to ibrutinib or 3 out of 5 weeks per cycle

Also known as: jakafi

Ibrutinib plus Ruxolitinib

ibrutinib DRUG

patients will be taking ibrutinib for at least 6 months and will continue to take it at the same dose and schedule while taking ruxolitinib

Also known as: imbruvica

Ibrutinib plus Ruxolitinib

Eligibility Criteria

• Age: 19 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.
• CLL currently being treated with Ibrutinib due to relapsed/refractory disease or primary del17p cytogenetic lesions at a daily dose of 420 mg and:
• failure of plasma b2M levels to decrease below 2.5 mg/L after 6 months after starting Ibrutinib.
• persistent lymphocytosis (\>5x106 cells/L) and splenomegaly or lymphadenopathy (marker node \>1.5 cm on CT scans) after 1 year of taking Ibrutinib.
• 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 \>75x109/L. Absolute neutrophil count (ANC)\>.75x109/L. Hemoglobin greater than or equal to 65 g/L
• Age \>18 years old
• Eastern Cooperative Oncology Group (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 hepatitis B virus (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 prior to alloSCT 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.
• 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.
• 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.
• 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 block without a pacemaker).
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Renal failure requiring dialysis or serum creatinine \>176.8 microM and patients with moderate (creatinine clearance of 30-50 ml/min) and severe (creatinine clearance\<30 ml/min) renal impairment with platelet counts less than 100,000/ml.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Novartis: collaborator

Study Sites (2)

Sunnybrook Odette Cancer Center

Toronto, Ontario, M4N 3M5, Canada

Location

Sunnybrook Odette Cancer Center

Toronto, Ontario, M4N3M5, Canada

Location

Related Publications (5)

• Oppermann S, Lam AJ, Tung S, Shi Y, McCaw L, Wang G, Ylanko J, Leber B, Andrews D, Spaner DE. Janus and PI3-kinases mediate glucocorticoid resistance in activated chronic leukemia cells. Oncotarget. 2016 Nov 8;7(45):72608-72621. doi: 10.18632/oncotarget.11618.

  PMID: 27579615 RESULT

• Spaner DE, Wang G, McCaw L, Li Y, Disperati P, Cussen MA, Shi Y. Activity of the Janus kinase inhibitor ruxolitinib in chronic lymphocytic leukemia: results of a phase II trial. Haematologica. 2016 May;101(5):e192-5. doi: 10.3324/haematol.2015.135418. Epub 2016 Jan 27. No abstract available.

  PMID: 26819050 RESULT

• Xia M, Luo TY, Shi Y, Wang G, Tsui H, Harari D, Spaner DE. Effect of Ibrutinib on the IFN Response of Chronic Lymphocytic Leukemia Cells. J Immunol. 2020 Nov 15;205(10):2629-2639. doi: 10.4049/jimmunol.2000478. Epub 2020 Oct 16.

  PMID: 33067379 DERIVED

• Spaner DE, McCaw L, Wang G, Tsui H, Shi Y. Persistent janus kinase-signaling in chronic lymphocytic leukemia patients on ibrutinib: Results of a phase I trial. Cancer Med. 2019 Apr;8(4):1540-1550. doi: 10.1002/cam4.2042. Epub 2019 Mar 7.

  PMID: 30843659 DERIVED

• Shi Y, Wang G, Muhowski EM, McCaw L, Wang C, Bjarnason G, Woyach JA, Spaner DE. Ibrutinib reprograms the glucocorticoid receptor in chronic lymphocytic leukemia cells. Leukemia. 2019 Jul;33(7):1650-1662. doi: 10.1038/s41375-019-0381-4. Epub 2019 Jan 29.

  PMID: 30696950 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ruxolitinib; ibrutinib

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

Study Officials

• David E Spaner, MD

  Sunnybrook Odette Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Scientist

Study Record Dates

• First Submitted: September 19, 2016
• First Posted: September 23, 2016
• Study Start: March 1, 2017
• Primary Completion: December 1, 2018
• Study Completion: August 1, 2019
• Last Updated: March 13, 2017

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (2)