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LeukemiaPhase 2NCT02481297

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

A Phase 2 study testing Lirilumab and Rituximab in people with Leukemia and Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Lirilumab and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
23 Jun 2015to 15 Aug 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Concurrent use of investigational therapeutic agent
  • Patients may not receive other concurrent chemotherapy, radiotherapy, or immunotherapy. Localized radiotherapy to an area not compromising bone marrow function does not apply.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Lirilumab (Anti-KIR mAb) Combined With Rituximab for Relapsed, Refractory or High-risk Untreated Patients With Chronic Lymphocytic Leukemia (CLL)

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.

Read the detailed description

Study Treatment:

Each study cycle is 28 days.

You will receive rituximab by vein over about 4-6 hours on Days 1,8, 15, and 22 of Cycle 1. After Cycle 1, you will receive rituximab on Day 1 of Cycles 2-12.

You will also receive lirilumab by vein over about 1 hour on Day 1 of each cycle.

Study Visits:

On Days 1, 8, 15, and 22 of Cycles 1 and 2 and then about every 2 weeks during Cycles 3-6:

  • You will have a physical exam. You will not have this exam on Days 8 and 22 of Cycle 2.
  • Blood (about 2 tablespoons) will be drawn for routine tests. If the doctor thinks it is needed, more blood may need to be drawn and you may need to have these tests performed more often. The study doctor will tell you if more blood will be drawn or if you will have this blood draw repeated.

On Day 1 of each cycle, if you can become pregnant, blood (about 1 tablespoon) or urine will be collected for a pregnancy test.

On Day 28 of Cycles 3 and 6:

  • You will have physical exam.
  • Blood (about 2 tablespoons) will be drawn for routine tests. This routine blood draw may include a pregnancy test if you can become pregnant. Urine may also be collected for this pregnancy test.
  • You will have a bone marrow aspiration/biopsy to check the status of the disease.
  • You will have a computerized tomography (CT) or positron emission tomography (PET) scan.

At least 1 time each month after Cycle 7:

  • You will have physical exam.
  • Blood (about 2 tablespoons) will be drawn for routine tests.

At least 1 time every 3 months after Cycle 7:

  • Urine will be collected for routine tests. This routine urine collection will include a pregnancy test, if you can become pregnant. Blood (about 1 tablespoon) may also be drawn for this pregnancy test.
  • You will have a bone marrow aspiration/biopsy to check the status of the disease.
  • You will have a CT or PET scan.

Any time that the doctor thinks it is needed while you are on study, you will have blood draws, CT or PET scans, and/or bone marrow aspirations/biopsies to check the status of the disease and/or to monitor your health.

If the doctor thinks it is acceptable, you may be able to have some of these tests, such as routine blood and urine collections, performed at a local lab or clinic closer to your home. The results will be sent to the study doctor for review. Ask the study staff or study doctor about this possibility.

Length of Study:

You may receive up to 12 cycles of rituximab and up to 24 cycles of lirilumab. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after about 1 year of follow-up visits.

End-of-Study Visit:

Within 30 days after your last dose of study drug:

  • You will have a physical exam.
  • Blood (about 2-3 tablespoons) will be drawn for routine tests.
  • If the doctor thinks it is needed, you will have a bone marrow aspirate to check the status of the disease.
  • If the doctor thinks it is needed, you will have a CT or PET scan.

Follow-Up Visits:

After your end-of-study visit, you will have the following tests and procedures performed.

One (1) time each month for up to 1 year:

  • You will have a physical exam.
  • Blood (about 2-3 tablespoons) will be drawn for routine tests.

One (1) time every 3-6 months for up to 1 year, if the doctor thinks it is needed:

  • You will have a bone marrow aspirate to check the status of the disease.
  • You will have a CT scan or a PET scan.

If you start a new type of anticancer treatment during the year after your last dose of study drugs, you will stop having these follow-up visits.

This is an investigational study. Lirilumab is not FDA approved or commercially available. Rituximab is FDA approved and commercially available for the treatment of CLL. The use of these drugs in combination to treat CLL/SLL is considered investigational. The study doctor can explain how the drugs are designed to work.

Up to 48 participants will be enrolled in this study. All will take part at MD Anderson.

Being tested
Lirilumab, Rituximab
Keywords
Leukemia, Chronic Lymphocytic Leukemia, CLL, Refractory/Relapsed, Untreated with high-risk molecular features, Small lymphocytic leukemia, SLL, Lirilumab, Rituximab, Rituxan
Medical subject headings
Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Lymphoid, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LirilumabDrug

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

  • RituximabDrug

    Also called Rituxan

    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.

Study groups in NCT02481297
Study groupRoleWhat they receive
Cohort 1: Refractory/Relapsed After Prior TherapyExperimentalParticipants 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.
Receives: Drug: Lirilumab; Drug: Rituximab
Cohort 2: Untreated with High-rRisk mMolecular FeaturesExperimentalParticipants 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.
Receives: Drug: Lirilumab; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 months

Secondary outcomes (2)
  1. Overall Survival

    Time from date of treatment start until date of death due to any cause or last Follow-up.

    Measured: Up to 4 years

  2. Progression Free Survival

    Time from date of treatment start until the date of first objective documentation of disease-relapse.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2015 (estimated)
  2. Study start23 Jun 2015
  3. Primary completion15 Aug 2019
  4. Study completion15 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02481297
Sponsor's protocol ID
2014-0933
Other IDs
NCI-2015-01113
Status last verified
May 2020
First submitted
23 Jun 2015
Last updated
28 May 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lirilumab and Rituximab in people with Leukemia and Chronic Lymphocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Participants With a Response (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2020.

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