Lenalidomide and Rituximab as Treatment of Chronic Lymphocytic Leukemia

NCT00759603 | Completed Phase 2 Results DMC

• 2 other identifiers: 2007-0208NCI-2012-01674
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of lenalidomide and rituximab can help to control Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) in patients who have already received therapy. The safety of this drug combination will also be studied.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Leukemia; CLL; Chronic Lymphocytic Leukemia; SLL; Small Lymphocytic Lymphoma; Lenalidomide; Revlimid; Rituximab; Rituxan

Outcome Measures

Primary Outcomes (1)

• Overall Participant Response Rate: Percentage of Participants With Complete + Partial Response According to Revised National Cancer Institute-sponsored Working Group Guidelines

  Complete response: Absence lymphadenopathy, hepatomegaly or splenomegaly \& constitutional symptoms; Normal complete blood count (CBC) exhibited by polymorphonuclear leukocytes\>1500/µL, platelets\>100,000/µL, hemoglobin\>11.0 g/dL (untransfused); lymphocyte count \<5,000/µL; Bone marrow aspirate \& biopsy normocellular for age with \<30% nucleated cells lymphocytes; Absence Lymphoid nodules. Fulfillment CR criteria after induction with exception of treatment related persistent cytopenia \& bone marrow lymphoid nodules both considered partial response; Partial response: Requires 50% decrease in peripheral lymphocytes from pre-treatment, 50% reduction in lymphadenopathy, \&/or 50% reduction in splenomegaly/hepatomegaly for 2+ months from therapy completion. Additionally one following from pre-treatment: Polymorphonuclear leukocytes 1,500/µL or 50% improvement; Platelets\>100,000/µL or 50% improvement; Hemoglobin\>11.0 g/dL (untransfused) or 50% improvement.

  Responses assessed after 12 cycles, up to 48 weeks with interim assessments performed after 3, 6 and 12 cycles.

Study Arms (1)

Lenalidomide + Rituximab

EXPERIMENTAL

Oral Lenalidomide 10 mg/day started on Day 9 of cycle 1; Rituximab 375 mg/m\^2 intravenously on Day 1, Day 8, Day 15 and Day 22 then continued once every four weeks during cycles 3-12 (+ 7 days). Rituximab not given in Cycle 2. Treatment duration twelve cycles.

Drug: Lenalidomide; Drug: Rituximab

Interventions

Lenalidomide DRUG

Started on Day 9 of Cycle 1 at the dose of 10 mg/day and continued daily. Treatment duration will be twelve cycles.

Also known as: Revlimid ®

Lenalidomide + Rituximab

Rituximab DRUG

Dose of 375 mg/m\^2 given intravenously on Day 1, Day 8, Day 15 and Day 22 then continued once every four weeks during cycles 3-12 (+ 7 days). Rituximab not given in Cycle 2.

Also known as: Rituxan®

Lenalidomide + Rituximab

Eligibility Criteria

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

You may qualify if:

• Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with active disease.
• Patients must be age 18 or over at the signing of consent and must understand and voluntarily sign an informed consent.
• Prior treatment with purine analog based chemotherapy or chemoimmunotherapy.
• Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0-2.
• Adequate renal function indicated by serum creatinine less or equal to 2 mg/dl. Adequate hepatic function indicated as total bilirubin less or equal to 2 mg/dl and ALT less or equal to two times the upper limit of normal.
• Disease free of prior malignancies for 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test (sensitivity of at least 50 milli-International unit (mIU/mL) 10-14 days prior to starting lenalidomide. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Continued from Criteria #7. FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts talking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
• Continued from Criteria #8: Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
• Men must agree not to father a child. They must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a vasectomy. They will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure. They must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from the study.
• Continued from Criteria #10: Counseling about the requirement for latex condom use during sexual contact with females of childbearing potential and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded not to share study drug and to not donate blood, sperm, or semen (during study participation and for 28 days following discontinuation from the study).

You may not qualify if:

• Known sensitivity to lenalidomide or other thalidomide derivatives or rituximab.
• Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood).
• Known positivity for HIV or active hepatitis (B or C).
• Pregnant or breast feeding females.
• History of tuberculosis treated within the last five years or recent exposure to tuberculosis.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk if he/she were to participate in the study.
• Patients with a recent history of deep vein thrombosis (DVT) or pulmonary embolus (PE), in the six months prior to enrollment are not eligible for this study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Takahashi K, Hu B, Wang F, Yan Y, Kim E, Vitale C, Patel KP, Strati P, Gumbs C, Little L, Tippen S, Song X, Zhang J, Jain N, Thompson P, Garcia-Manero G, Kantarjian H, Estrov Z, Do KA, Keating M, Burger JA, Wierda WG, Futreal PA, Ferrajoli A. Clinical implications of cancer gene mutations in patients with chronic lymphocytic leukemia treated with lenalidomide. Blood. 2018 Apr 19;131(16):1820-1832. doi: 10.1182/blood-2017-11-817296. Epub 2018 Jan 22.

  PMID: 29358183 DERIVED

• Badoux XC, Keating MJ, Wen S, Wierda WG, O'Brien SM, Faderl S, Sargent R, Burger JA, Ferrajoli A. Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2013 Feb 10;31(5):584-91. doi: 10.1200/JCO.2012.42.8623. Epub 2012 Dec 26.

  PMID: 23270003 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia

Interventions

Lenalidomide; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; 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

Results Point of Contact

• Title: Alessandra Ferrajoli, MD/Professor, Leukemia
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Alessandra Ferrajoli, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2008
• First Posted: September 25, 2008
• Study Start: September 1, 2008
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: August 27, 2015
• Results First Posted: August 27, 2015

Record last verified: 2015-07

Locations

US (1)