Clinical Trials /

A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL

NCT02135133

Description:

This research study is evaluating a combination of drugs called Ofatumumab and Idelalisib as a possible treatment for Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Leukemia (SLL). The main purpose of this study is to examine the combination of the two drugs, Ofatumumab and Idelalisib, in participants who have been diagnosed with CLL/SLL and have not previously received treatment but do require treatment. The investigators hope to observe how participants' disease will be impacted by this treatment and whether they will benefit more from combining these drugs together rather than taking them separately. Both of these drugs have been used in treatment for CLL / SLL and information from those research studies suggests that these drugs may help patients with CLL/SLL. Ofatumumab is an antibody engineered in the lab against CD20, a protein on the surface of CLL cells, which is expressed in CLL. An antibody is a molecule your body creates to identify foreign substances so that it can destroy them. Ofatumumab has been FDA approved for treatment of CLL/SLL that has relapsed or progressed on other therapies. Idelalisib is a drug that blocks one of the signals inside the cells that cause this type of cancer to grow and survive. The investigators hope that combining Ofatumumab with Idelalisib will stop the growth of disease. In this research study, the investigators are evaluating the side effects of combining these two drugs, gathering information on the CLL/SLL disease process and how the study affects the patient's cells, as well as assessing the outcome of the disease. This combination of drugs has been previously tested, and appeared to be well tolerated.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

A Study of Idelalisib (<span class="go-doc-concept go-doc-intervention">GS1101</span>, CAL101) + <span class="go-doc-concept go-doc-intervention">Ofatumumab</span> in Previously Untreated CLL/SLL

Title

  • Brief Title: A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL
  • Official Title: A Phase II Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Leukemia (SLL)
  • Clinical Trial IDs

    NCT ID: NCT02135133

    ORG ID: 13-309

    Trial Conditions

    Chronic Lymphocytic Leukemia

    Small Lymphocytic Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    Idelalisib GS1101 Idelalisib & Ofatumumab
    Ofatumumab Arzerra Idelalisib & Ofatumumab

    Trial Purpose

    This research study is evaluating a combination of drugs called Ofatumumab and Idelalisib as
    a possible treatment for Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Leukemia
    (SLL).

    The main purpose of this study is to examine the combination of the two drugs, Ofatumumab
    and Idelalisib, in participants who have been diagnosed with CLL/SLL and have not previously
    received treatment but do require treatment. The investigators hope to observe how
    participants' disease will be impacted by this treatment and whether they will benefit more
    from combining these drugs together rather than taking them separately. Both of these drugs
    have been used in treatment for CLL / SLL and information from those research studies
    suggests that these drugs may help patients with CLL/SLL.

    Ofatumumab is an antibody engineered in the lab against CD20, a protein on the surface of
    CLL cells, which is expressed in CLL. An antibody is a molecule your body creates to
    identify foreign substances so that it can destroy them. Ofatumumab has been FDA approved
    for treatment of CLL/SLL that has relapsed or progressed on other therapies. Idelalisib is a
    drug that blocks one of the signals inside the cells that cause this type of cancer to grow
    and survive. The investigators hope that combining Ofatumumab with Idelalisib will stop the
    growth of disease.

    In this research study, the investigators are evaluating the side effects of combining these
    two drugs, gathering information on the CLL/SLL disease process and how the study affects
    the patient's cells, as well as assessing the outcome of the disease. This combination of
    drugs has been previously tested, and appeared to be well tolerated.

    Detailed Description

    Before the research starts (screening): After signing the consent form, the participant will
    be asked to undergo some screening tests or procedures to find out if they are eligible to
    be in this research study. Many of these tests and procedures are likely to be part of
    regular cancer care and may be done even if it turns out that the participant does not take
    part in the research study. If the participant has had some of these tests or procedures
    recently, they may or may not have to be repeated.

    - A medical history, which includes questions about the participant's health, current
    medications, and any allergies.

    - Physical examination, which includes vital signs, height, weight, and disease
    assessment by the size of the participant's spleen, liver, and lymph nodes.

    - Performance status, which evaluates how the participant is able to carry on with their
    usual activities.

    - An assessment of the patient's tumor by CT (Computerized Tomography) scan, MRI or PET
    (Positron Emission Tomography) scans,

    - Bone marrow aspirate and biopsy: A study tube (plastic cylinder container that contains
    biopsy material) will be drawn during this biopsy to further assess the participant's
    disease status.

    - Blood tests, a maximum of 24 teaspoons will be collected.

    - Urine test.

    - A blood pregnancy test

    - A Hepatitis B and C test, will require blood sample.

    If these tests show that the participant is eligible to participate in the research study,
    then the participant will be begin will begin the study treatment. If you do not meet the
    eligibility criteria, the participant will not be able to participate in this research
    study.

    Additional research procedures to be performed at the time of screening:

    Blood tests, including baseline tests so that the investigators can measure any additional
    effect of the study drug and disease status

    After the screening procedures confirm that you are eligible to participate in the research
    study:

    If you take part in this research study, the participant will be given a study drug-dosing
    diary for each treatment cycle. Each treatment cycle lasts 28 days. The diary will also
    include special instructions for taking the study drugs.

    - Study Drugs: The participant will first be given Idelalisib daily for two cycles of 28
    days each. Idelalisib will be given orally. Once the participant completes 2 cycles of
    Idelalisib, then the participant will start to receive a combination of Ofatumumab and
    Idelalisib. This regimen will continue weekly to complete 8 weeks (two more cycles).
    This will be followed by monthly Ofatumumab and Idelalisib to complete 4 additional
    cycles (eight total). The overall treatment period will therefore be 8 months,
    comprised of two months of Idelalisib followed by 6 months of Ofatumumab with
    Idelalisib. After completing the 8-month treatment, the participant will likely
    continue Idelalisib. Restaging with CT scans will happen after Cycle 2, 4, and a final
    restage will occur 2 months after the completion of Ofatumumab. There will be a tumor
    response assessment done during a physical exam after Cycle 8.

    - Clinical Exams: During all cycles the participant will have a physical exam and will
    be asked questions about their general health and specific questions about any problems
    that they might be having and any medications they may be taking.

    - Scans (or Imaging tests): The investigator will assess the participant's tumor by CT
    scan. Restaging with CT scans will happen after Cycle 2, 4, and a final restage will
    occur 2 months after the completion of Ofatumumab.

    - Bone marrow aspirate and biopsy: will be conducted to see if the bone marrow has tumor
    cells. A study tube will be drawn during this biopsy to further assess the patient's
    disease status

    - Blood tests

    Additional Blood Tests:

    Blood Tests will be performed throughout the study so that the Investigator can measure any
    additional effect of the study drug and disease status. These tests will be taken on the
    days listed below before the participant receive study drug, on some days additional blood
    will be drawn after they receive study drug.

    Cycle 3 Day 1 Cycle 3 Day 8 Cycle 3 Day 15 Cycle 4 Day 21 (last weekly Ofatumumab dose)
    Cycle 5 Day 1 (first monthly Ofatumumab dose) Cycle 8 Day 1 (last monthly Ofatumumab dose) 2
    months after Ofatumumab therapy completed 6 months after Ofatumumab therapy completed

    Planned Follow-up:

    Once the participant has completed the study treatment, the participant will be monitored
    until they start a new type of treatment or are removed from the study. During this time the
    participant will meet with your research physician every 3 or 6 months.

    The investigator would like to keep track of the participant's medical condition for the
    rest of their life. The investigator would like to do this by calling the participant on
    the telephone once a year to see how the participant is doing. Keeping in touch with the
    participant and checking their condition every year helps the investigator look at the
    long-term effects of the research study.

    Trial Arms

    Name Type Description Interventions
    Idelalisib & Ofatumumab Experimental Idelalisib will be given orally continuously at 150 mg BID. On day 57, ofatumumab will begin with the 300 mg dose, given after idelalisib is taken. Ofatumumab will then be administered at 1000 mg weekly to complete 8 weeks (days 64, 71, 78, 85, 92, 99, 106) throughout Cycles 3 and 4. This will be followed by monthly ofatumumab on weeks 20, 24, 28, 32 to complete 4 additional cycles (5-8). The overall induction treatment period will then be 8 months, comprised of two months of single agent idelalisib followed by 6 months of ofatumumab with idelalisib. After the completion of the induction treatment, idelalisib will continue indefinitely in arbitrarily defined 28 day cycles in all participants who have not had excessive toxicity and do not have progressive disease. Idelalisib, Ofatumumab

    Eligibility Criteria

    Inclusion Criteria:

    - Participants must meet the following criteria on screening examination to be eligible
    to participate in the study:

    - Subjects must have CLL / SLL, as documented by a history at some point of an absolute
    peripheral blood B cell count > 5000, with a monoclonal B cell population
    co-expressing CD19, CD5, and CD23, or if CD23 negative, then documentation of the
    absence of t(11;14) or cyclin D1 overexpression. Alternatively patients with
    lymphadenopathy in the absence of circulating disease will also be eligible for this
    study if lymph node biopsy establishes the diagnosis of CLL with the above
    immunophenotype.

    - Participants must have measurable disease (lymphocytosis > 5,000, or palpable or CT
    measurable lymphadenopathy > 1.5 cm, or bone marrow involvement >30%).

    - Subjects must not have received any prior systemic therapy for CLL and currently have
    an indication for treatment as defined by the IWCLL 2008 Guidelines:

    - Massive or progressive splenomegaly; OR

    - Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR

    - Grade 2 or 3 fatigue; OR

    - Fever 100.5F or night sweats for greater than 2 weeks without documented
    infection; OR

    - Presence of weight loss 10% over the preceding 6 months; OR

    - Progressive lymphocytosis with an increase of 50% over a 2-month period or an
    anticipated doubling time of less than 6 months; OR

    - Evidence of progressive marrow failure as manifested by the development of or
    worsening of anemia and or thrombocytopenia.

    - ECOG performance status <2 (see Appendix A).

    - Age 18 years. Because no dosing or adverse event data are currently available on
    the use of idelalisib or ofatumumab in participants <18 years of age, children are
    excluded from this study.

    - Participants must have normal organ and marrow function as defined below:

    - creatinine <2.0 times upper normal limit, total bilirubin <1.5 times upper normal
    limit (unless due to disease involvement of liver, hemolysis or a known history of
    Gilbert's disease)

    - ALT <2.5 times upper normal limit (unless due to disease involvement of liver)
    alkaline phosphatase <2.5 times upper normal limit (unless due to disease involvement
    of the liver or bone marrow)

    - Ability to understand and the willingness to sign a written informed consent
    document.

    Exclusion Criteria:

    - Participants who exhibit any of the following conditions at screening will not be
    eligible for admission into the study.

    - Participants who have had any prior systemic therapy for CLL, or chemotherapy or
    radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) for some other
    indication prior to entering the study or those who have not recovered from adverse
    events due to agents administered more than 4 weeks earlier.

    - History of severe allergic reactions attributed to compounds of similar chemical or
    biologic composition to ofatumumab or idelalisib.

    - Subjects who have current active hepatic or biliary disease (with exception of
    participants with Gilbert's syndrome, asymptomatic gallstones, liver metastases or
    stable chronic liver disease per investigator assessment)

    - Treatment with any known non-marketed drug substance or experimental therapy within 5
    terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently
    participating in any other interventional clinical study

    - Other past or current malignancy that could interfere with the interpretation of
    outcome. Subjects who have been free of active malignancy for at least 2 years, or
    have a history of completely resected non-melanoma skin cancer or successfully
    treated in situ carcinoma, or whose malignancy will not interfere with the
    interpretation of study results, are eligible.

    - Chronic or current infectious disease requiring systemic antibiotics, antifungal, or
    antiviral treatment such as, but not limited to, chronic renal infection, chronic
    chest infection with bronchiectasis, tuberculosis and active Hepatitis C.

    - History of significant cerebrovascular disease in the past 6 months or ongoing event
    with active symptoms or sequelae

    - Known HIV positive. HIV-positive individuals on combination antiretroviral therapy
    are ineligible because of the potential for pharmacokinetic interactions with
    idelalisib. In addition, these individuals are at increased risk of lethal infections
    when treated with marrow-suppressive therapy. Appropriate studies will be undertaken
    in participants receiving combination antiretroviral therapy when indicated.

    - Clinically significant cardiac disease including unstable angina, acute myocardial
    infarction within six months prior to randomization, congestive heart failure (NYHA
    III-IV), and arrhythmia unless controlled by therapy, with the exception of extra
    systoles or minor conduction abnormalities.

    - Significant concurrent, uncontrolled medical condition including, but not limited to,
    renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
    psychiatric disease which in the opinion of the investigator may represent a risk for
    the participant.

    - Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In
    addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB
    DNA test will be performed and if positive the subject will be excluded.

    - If HBV DNA is negative, subject may be included but must undergo HBV DNA PCR testing
    at least every 2 months from the start of treatment until 12 months post treatment.
    Prophylactic antiviral therapy may be initiated at the discretion of the
    investigator.

    - Positive serology for hepatitis C (HC) defined as a positive test for HepC Ab, in
    which case reflexively perform an HC RIBA immunoblot assay or hepatitis C viral load
    to confirm the result. If the confirmatory test is negative the subject will be
    eligible.

    - Pregnant or lactating women.

    - Women of childbearing potential, including women whose last menstrual period was less
    than one year prior to screening, unable or unwilling to use adequate contraception
    from study start to 30 days after the last dose of protocol therapy. Adequate
    contraception is defined as hormonal birth control, intrauterine device, double
    barrier method or total abstinence.

    - Male subjects unable or unwilling to use adequate contraception methods from study
    start to 30 days after the last dose of protocol therapy.

    - Participants using concomitant corticosteroids are allowed as long as the subject is
    on the equivalent of 20mg/day or less of prednisone and has been on a stable dose for
    at least two weeks prior to initiating therapy.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Response Rate of ofatumumab and idelalisib in previously untreated CLL/SLL participants in need of therapy

    Secondary Outcome Measures

    CR rate and PFS of ofatumumab and idelalisib.

    ORR, CR rate and rate of nodal PR with lymphocytosis for idelalisib given alone for two months of therapy to previously untreated participants

    Frequency of lymphocytosis with single agent idelalisib in previously untreated participants

    Frequency of serious adverse events while on treatment with idelalisib and ofatumumab

    Correlation of clinical response with known CLL molecular prognostic factors including FISH, IGHV, ZAP-70.

    Contribution of CT scans to response assessment

    Correlation of serum ofatumumab and/or idelalisib levels in vivo with response.

    Cell surface marker phenotype of circulating CLL cells.

    Impact of in vivo treatment with idelalisib on CLL cell sensitivity to therapy with antibodies or other kinase inhibitors.

    Pharmacodynamic markers of PI3 kinase inhibition including AKT phosphorylation, production of T cell chemokines and response to CXCR 4/5.

    Correlation of genetic alterations in PIK3CA or PIK3CD or other genes with response or resistance ot idelalisib

    Influence of idelalisib treatment on intrinsic innate immune suppression and on regulatory T cells.

    Prediction of response and resistance to idelalisib through biochemical and genetic analysis of the PI3K pathway.

    Trial Keywords

    Chronic Lymphocytic Leukemia

    Small Lymphocytic Lymphoma