Lirilumab With Rituximab for Relapsed, Refractory or High-risk Untreated Chronic Lymphocytic Leukemia (CLL) Patients

NCT02481297 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0933NCI-2015-01113
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if lirilumab in combination with rituximab can help to control either CLL or Small lymphocytic lymphoma (SLL). The safety of the drug combination will also be studied.

Conditions

Leukemia; Chronic Lymphocytic Leukemia; Lymphocytic Leukemia

Keywords

Leukemia; Chronic Lymphocytic Leukemia; CLL; Refractory/Relapsed; Untreated with high-risk molecular features; Small lymphocytic leukemia; SLL; Lirilumab; Rituximab; Rituxan

Outcome Measures

Primary Outcomes (1)

• Participants With a Response

  Response is defined as complete remission (CR), complete remission with incomplete marrow recovery (CRi) or partial remission (PR) that occurs during the first 6 months of therapy. CR requires the absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts. CRi is Complete remission with incomplete bone marrow recovery. PR, defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts

  6 months

Secondary Outcomes (2)

• Overall Survival

  Up to 4 years

• Progression Free Survival

  Up to 4 years

Study Arms (2)

Cohort 1: Refractory/Relapsed After Prior Therapy

EXPERIMENTAL

Participants receive Rituximab 375 mg/m2 by vein weekly for the first 4 weeks (Days 1, 8, 15, 22), then with start of each course. Lirilumab 3 mg/kg by vein given on Day 1 of each cycle. Rituximab given for the first 12 cycles and Lirilumab continues for up to 24 cycles. Each cycle is 4 weeks.

Drug: Lirilumab; Drug: Rituximab

Cohort 2: Untreated with High-rRisk mMolecular Features

EXPERIMENTAL

Participants receive Rituximab 375 mg/m2 by vein weekly for the first 4 weeks (Days 1, 8, 15, 22), then with start of each course. Lirilumab 3 mg/kg by vein given on Day 1 of each cycle. Rituximab given for the first 12 cycles and Lirilumab continues for up to 24 cycles. Each cycle is 4 weeks.

Drug: Lirilumab; Drug: Rituximab

Interventions

Lirilumab DRUG

3 mg/kg by vein given on Day 1 of each 28 day cycle.

Cohort 1: Refractory/Relapsed After Prior Therapy; Cohort 2: Untreated with High-rRisk mMolecular Features

Rituximab DRUG

375 mg/m2 by vein weekly for the first 4 weeks on Days 1,8, 15, and 22 of Cycle 1. After Cycle 1, given on Day 1 of Cycles 2 - 12.

Also known as: Rituxan

Cohort 1: Refractory/Relapsed After Prior Therapy; Cohort 2: Untreated with High-rRisk mMolecular Features

Eligibility Criteria

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

You may qualify if:

• Patients will have a diagnosis of CLL or SLL who meet one or more criteria for active disease as defined by the International Working Group for CLL (IWCLL) and are: a. Cohort 1: refractory to and/or relapsed after at least one prior therapy OR b. Cohort 2: untreated patients with high-risk molecular features such as del(17p), mutated TP53, del(11q), unmutated IGHV gene, or are \>65 years of age
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) Performance Status \</=2
• Patients must have adequate renal and hepatic function: Serum bilirubin \</=1.5 x upper limit of normal (ULN). For patients with Gilbert's disease, serum bilirubin up to \</=3 x ULN is allowed provided normal direct bilirubin; Serum creatinine ≤1.5 x ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \</=3 x ULN
• Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (Beta-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception method during the study and for 12 months following the last dose of the study drugs. Females of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks following the last dose of study drugs.
• Patients or their legally authorized representative must provide written informed consent.

You may not qualify if:

• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized prostate cancer. If patients have another malignancy that was treated within the last 2 years, such patients may be enrolled if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center and after consultation with the Principal Investigator.
• Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 4 weeks prior to the first dose of the study drugs. For oral targeted therapies (such as ibrutinib, idelalisib, venetoclax), a washout of 3 days is allowed. Note: Prior treatment with anti CD20 monoclonal antibody, anti CD52 monoclonal antibody and lenalidomide are allowed. Prior treatment with anti-CTLA-4 and anti-PD1 therapies is allowed after a wash-out of 5 half-lives.
• Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 2 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
• History of stroke or cerebral hemorrhage within 2 months.
• Patients who have uncontrolled hypertension (defined as sustained systolic blood pressure \>/= 160 mmHg or diastolic \>/= 100 mmHg).
• Known evidence of active cerebral/meningeal CLL. Patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration.
• Active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring steroid therapy.
• Patients with autoimmune diseases are excluded: Patients with a history of Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus, Wegener's granulomatosis).
• Patients with previous allogeneic stem cell transplant (SCT) within 6 months or with active acute or chronic graft-versus host disease are excluded. Patients must be off immunosuppression for graft versus host disease (GVHD) for at least 60 days before Cycle 1 Day 1.
• Patients with organ allografts (such as renal transplant) are excluded.
• History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), auto immune, or grade 3-4 drug-related hepatitis).
• Patients who are on high-dose steroids (doses \>10mg/day of prednisone or equivalent) or immune suppression medications. Note: Patients on high-dose steroids (doses \>10mg/day of prednisone or equivalent) or immune suppression medications are eligible provided these drugs are discontinued at least 3 days prior to starting on the study drugs.
• Patients with uncontrolled active infection (viral, bacterial, and fungal) are not eligible.
• Current or chronic hepatitis B or C infection, or known seropositivity for HIV.
• Patient is pregnant or breast-feeding.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Recurrence

Interventions

lirilumab; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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: Dr. Nitin Jain/Associate Professor
• Organization: The University of Texas MD Anderson Cancer Center

njain@mdanderson.org

713-745-6080

Study Officials

• Nitin Jain, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: June 25, 2015
• Study Start: June 23, 2015
• Primary Completion: August 15, 2019
• Study Completion: August 15, 2019
• Last Updated: May 28, 2020
• Results First Posted: May 26, 2020

Record last verified: 2020-05

Locations

US (1)