Phase I Study of Lenalidomide, Rituximab and Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

NCT02200848 | Terminated Phase 1 DMC

• 1 other identifier: NCI#9540
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for subjects diagnosed with recurrent or relapsed CLL/SLL. The purpose of this study is to test the safety of the combination of the drugs lenalidomide and ibrutinib at different dose levels, in combination with the drug rituximab. We want to find out what effects, good and/or bad, they have on patients with CLL/SLL. The hypothesis of the study is that it will be safe to give the three drugs in combination and the information learned from this trial will be used to study the 3 drug combination is a larger future trial.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Lenalidomide; Ibrutinib; Rituximab; CLL; SLL

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II dose

  The dose at which less than 2 of 6 patients experience a dose limiting toxicity

  1year

Secondary Outcomes (2)

• Safety

  2 years

• Antitumor efficacy

  2 years

Study Arms (1)

Lenalidomide, Ibrutinib, Rituximab

EXPERIMENTAL

Rituximab on day 1, lenalidomide days 1-21 and ibrutinib continuously for 6 cycles or until disease progression or intolerance to the combination. Single agent ibrutinib will then be continued until disease progression or intolerance.

Drug: Lenalidomide, Ibrutinib, Rituximab

Interventions

Lenalidomide, Ibrutinib, Rituximab DRUG

Dose level -2 Ibrutinib 280 mg; Lenalidomide 2.5 mg; Rituximab 375 mg/m2 Level -1 Ibrutinib 420 mg; Lenalidomide 2.5 mg; Rituximab 375 mg/m2 Level 1 Ibrutinib 420 mg; Lenalidomide 5 mg; Rituximab 375 mg/m2 Level 2 Ibrutinib 420 mg; Lenalidomide 10 mg; Rituximab 375 mg/m2 Level 3 Ibrutinib 420 mg; Lenalidomide 15 mg; Rituximab 375 mg/m2

Also known as: Ibrutinib, PCI-32765, NSC# 748645, Imbruvica, Lenalidomide, alpha-[3-aminophthalimido] glutarimide, Revlimid, CC-5013, NSC#703813, Rituximab, IDEC-C2B8, Rituxan

Lenalidomide, Ibrutinib, Rituximab

Eligibility Criteria

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

You may qualify if:

• Previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma that requires treatment
• No prior systemic treatment within 4 weeks of enrollment
• No corticosteroids within 2 weeks prior to study entry
• Measurable disease must be present
• No concomitant anti-cancer therapies
• ECOG status \</= 2
• Patients with HIV infection are eligible
• Patients with treated CLL or SLL in CNS are eligible
• Non-pregnant and non-nursing
• Life expectancy greater than 60 days
• Adequate bone marrow, kidney and liver function
• No major surgery within 28 days or minor surgery within 5 days of starting treatment

You may not qualify if:

• History od Richter's transformation
• History of prior allogeneic transplant
• Radioimmunotherapy within 1 year of enrollment
• Prior Bruton's tyrosine kinase inhibitor or lenalidomide
• History of allergic reactions to compounds similar to ibrutinib, lenalidomide or rituximab or hypersensitivity
• active or uncontrolled autoimmune hemolytic anemia or ITP
• Transfusion-dependent thrombocytopenia or bleeding disorders
• Active hepatitis B or C infections
• History of known Human Anti-Chimeric Antibody positivity
• History of erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome
• History of uncontrolled seizures
• Autoimmune disorder that requires active immunosuppression
• Stroke or intracranial hemorrhage within last 6 months
• History of congestive heart failure, myocardial infarction, unstable angina, uncontrolled arrhythmia or any Class 3 or 4 heart disease in the last 6 months
• No prior malignancy except if treated with curative intent with no active disease for more than 3 years; adequately treated non-melanoma skin cancer or cervical cancer in situ

Sponsors & Collaborators

• Georgetown University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (1)

• Ujjani C, Wang H, Skarbnik A, Trivedi N, Ramzi P, Khan N, Cheson BD. A phase 1 study of lenalidomide and ibrutinib in combination with rituximab in relapsed and refractory CLL. Blood Adv. 2018 Apr 10;2(7):762-768. doi: 10.1182/bloodadvances.2017015263.

  PMID: 29610115 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide; ibrutinib; Rituximab; glutarimide

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Chaitra Ujjani, MD

  Georgetown Lombardi Comprehsnive Cancer 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: July 22, 2014
• First Posted: July 25, 2014
• Study Start: April 1, 2014
• Primary Completion: March 27, 2017
• Study Completion: August 1, 2017
• Last Updated: January 12, 2018

Record last verified: 2017-05

Locations

US (1)