Lenalidomide, Ibrutinib, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma That Is Metastatic or Cannot Be Removed by Surgery
A Phase 1 Study of Lenalidomide and Ibrutinib in Combination With Rituximab in Relapsed and Refractory CLL and SLL
5 other identifiers
interventional
12
1 country
2
Brief Summary
This phase I trial studies the side effects and best dose of lenalidomide when given together with ibrutinib and rituximab in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that has come back (relapsed), has not responded well to prior treatments (refractory), has spread to other parts of the body (metastatic), or cannot be removed by surgery. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide together with ibrutinib and rituximab may kill more cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2014
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 20, 2014
CompletedFirst Submitted
Initial submission to the registry
May 30, 2014
CompletedFirst Posted
Study publicly available on registry
June 10, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 27, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
August 13, 2026
ExpectedMay 13, 2026
February 1, 2026
2.9 years
May 30, 2014
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Recommended phase II dose of lenalidomide and ibrutinib with rituximab based on the maximum tolerated dose and the assessment of any clinically relevant toxicity
Graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Up to 28 days
Secondary Outcomes (5)
Incidence of adverse events
Up to 30 days following the last dose of ibrutinib
Overall response rate
From the start of the treatment until disease progression/recurrence or death, assessed up to 10 years
Complete response rates
Up to 10 years
Duration of response
From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death, assessed up to 10 years
Progression-free survival
Time from start of treatment to time of progression or relapse or death, whichever occurs first, assessed up to 10 years
Study Arms (1)
Treatment (lenalidomide, ibrutinib, rituximab)
EXPERIMENTALPatients receive rituximab IV on day 1 (up to 6 cycles), lenalidomide PO QD on days 1-21 (up to 12 cycles), and ibrutinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECG on screening and CT scan or MRI, bone marrow biopsy and blood sample collection throughout the study.
Interventions
Undergo CT
Undergo ECG
Given PO
Given PO
Given IV
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo MRI
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; previously treated, pathologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that requires as per the National Cancer Institute (NCI) Working Group Guidelines for the treatment of CLL; the diagnosis of CLL is defined by the presence of 5 x 10\^9 clonal B-lymphocytes/L in the peripheral blood; clonality of the lymphocyte population is established with flow cytometry and the demonstration of the following surface markers: CD5, CD23, CD19, CD20 and the presence of either kappa or lambda immunoglobulins; the diagnosis of SLL may be made with the demonstration of \< 5 x 10\^9 clonal B-lymphocytes/L in the peripheral blood, with the clinical or radiographic features of enlarged lymph nodes or organomegaly, and the demonstration of SLL cells in the lymph node biopsy; institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression; patients may not have had a history of Richter's transformation
- No prior systemic therapy for CLL or SLL including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy), radiation therapy, within 4 weeks of enrollment; no prior carmustine (BCNU) or mitomycin C within 6 weeks of enrollment; no radioimmunotherapy within a year of enrollment; no corticosteroids administered within 2 weeks prior to study entry, except for maintenance therapy (=\< prednisone 20 mg daily or equivalent) for a non-malignant disease
- Patients may have had a prior autologous stem cell transplant; no prior history of allogeneic stem cell transplant
- Patients may have received prior lenalidomide as long as it has been at least two years since exposure and the patient may not have experienced a progression while receiving lenalidomide previously
- No Bruton's tyrosine kinase inhibitor at any point prior to enrollment
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib, lenalidomide or rituximab or hypersensitivity to murine proteins or to any component of rituximab
- Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass \> 1 cm is acceptable; lesions that are considered non-measurable include the following:
- Bone lesions (lesions if present should be noted)
- Ascites
- Pleural/pericardial effusion
- Lymphangitis cutis/pulmonis
- Bone marrow (involvement by SLL or CLL should be noted)
- No concomitant approved anti-cancer therapies or any investigational agents
- Patients with active or uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) are excluded; patients who have transfusion-dependent thrombocytopenia or bleeding/coagulation disorders that may increase the risk of life-threatening bleeding are excluded
- Eastern Cooperative Oncology Group (ECOG) performance status must be \< 2
- +36 more criteria
You may not qualify if:
- Chemotherapy =\< 21 days prior to first administration of study treatment and/or monoclonal antibody =\< 6 weeks prior to first administration of study treatment
- Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib
- Patients who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or patients who require continuous treatment with a strong CYP3A inhibitor
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or an infection requiring systemic antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; recent infections requiring systemic treatment need to have completed therapy \> 14 days before the first dose of study drug
- Pregnant and breastfeeding women are excluded from this study; pregnant women are excluded in this study because ibrutinib is a tyrosine kinase inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ibrutinib, breastfeeding should be discontinued if the mother is treated with ibrutinib
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are eligible; unless the patient's CD4 count is below the institutional lower limit of normal
- Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
- Presence of transfusion-dependent thrombocytopenia
- Patients requiring daily corticosteroids at a prednisone equivalent of \>= 20 mg daily should not be enrolled; if corticosteroids can be discontinued (or reduced to \< 20 mg per day of prednisone or equivalent), the discontinuation or dose reduction should be done at least 7 days prior to first dose
- History of prior malignancy, with the exception of the following:
- Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
- Adequately treated cervical carcinoma in situ without current evidence of disease
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kieron Dunleavy
MedStar Georgetown University Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 30, 2014
First Posted
June 10, 2014
Study Start
May 20, 2014
Primary Completion
March 27, 2017
Study Completion (Estimated)
August 13, 2026
Last Updated
May 13, 2026
Record last verified: 2026-02