Ruxolitinib in the Treatment of Chronic Lymphocytic Leukemia

NCT02015208 | Completed Phase 1 DMC

• 1 other identifier: CINC424XCA03T
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if Ruxolitinib, an inhibitor of cytokine-signaling, is effective in the treatment of patients with Chronic Lymphocytic Leukemia for whom conventional chemotherapy is either too toxic or ineffective.

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL; cytokine signaling; signal transduction inhibitors; elderly; p53

Outcome Measures

Primary Outcomes (1)

• Clinical response rate

  at 7 months

Secondary Outcomes (1)

• number of patients with adverse events

  participants will be followed for an average of 8 months

Other Outcomes (1)

• Effects of ruxolitinib on immune and leukemia cell numbers, JAK signaling, and circulating cytokine levels

  within 6 months of completing enrollment

Study Arms (1)

Ruxolitinib

EXPERIMENTAL

Ruxolitinib will be administered over a 28-day cycle, which will be repeated 6 more times in the absence of intolerable toxicity, disease progression, patient withdrawal of consent, or investigator decision to end therapy. The dose and schedule have been adapted from the product monograph for myelofibrosis. The starting dose will be 20 mg orally twice a day with normal .platelet and absolute neutrophil counts and no hepatic and renal impairment.

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

20 mg orally on day 1 to 21 of each 28 day cycle. Number of Cycles: 7 or until progression or unacceptable toxicity develops.

Also known as: jakafi

Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• Age greater than 65 years unless a 17p deletion is present in more than 20% of circulating tumor cells, in which case age can be younger than 65 years.
• Diagnosis of CLL meeting published diagnostic criteria.
• CLL requiring treatment on the basis of National Cancer Institute (NCI) working group criteria.
• Not previously treated with cytotoxic drugs or antibodies but may have received glucocorticoid monotherapy, local radiation, or splenectomy.
• Unfit for full dose FCR chemotherapy.
• Platelets \>50x10\*\*9/L. Neutrophils\>.75x10\*\*9/L.
• At least 1 lymph node \>1.5 cm or splenomegaly as detected by CT scan.

You may not qualify if:

• Fit for full-dose FCR as initial treatment.
• Progressive multifocal leukoencephalopathy (PML).
• Clinically significant bacterial, fungal, parasitic or viral infection, which require therapy.
• Richter's transformation or prolymphocytic leukemia.
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
• Prior exposure to chemotherapy for CLL with the exception of glucocorticoids, local radiation, or splenectomy.
• History of prior malignancy, with the exception of the following: i. Malignancy treated with curative intent and with no evidence of active disease for more than 2 years. ii. Adequately treated skin cancer. iii. Adequately treated cervical carcinoma in situ.
• Currently active clinically significant cardiovascular disease.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Renal failure requiring dialysis and patients with moderate and severe renal impairment with platelet counts less than 100,000/ml.
• Hepatic impairment.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Novartis: collaborator

Study Sites (1)

Sunnybrook Odette Cancer Center

Toronto, Ontario, M4N3M5, Canada

Location

Related Publications (2)

• Tomic J, Lichty B, Spaner DE. Aberrant interferon-signaling is associated with aggressive chronic lymphocytic leukemia. Blood. 2011 Mar 3;117(9):2668-80. doi: 10.1182/blood-2010-05-285999. Epub 2011 Jan 4.

  PMID: 21205928 BACKGROUND

• 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

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ruxolitinib

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, PhD

  Sunnybrook Health Sciences Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2013
• First Posted: December 19, 2013
• Study Start: April 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: September 26, 2016

Record last verified: 2016-09

Locations

CA (1)