Clinical Trials /

Atezolizumab, Obinutuzumab, and Ibrutinib in Treating Patients With Relapsed, Refractory, or Untreated High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT02846623

Description:

This phase II trial studies how well atezolizumab, obinutuzumab, and ibrutinib work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that has come back after a period of improvement, does not respond to treatment, or is high-risk and untreated. Immunotherapy with monoclonal antibodies, such as atezolizumab and obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab, obinutuzumab, and ibrutinib may work better in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Atezolizumab, Obinutuzumab, and Ibrutinib in Treating Patients With Relapsed, Refractory, or Untreated High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
  • Official Title: Atezolizumab (PD-L1 mAb) in Combination With Obinutuzumab and Ibrutinib for Patients With Relapsed, Refractory, or High-Risk Untreated Chronic Lymphocytic Leukemia (CLL)

Clinical Trial IDs

  • ORG STUDY ID: 2015-1097
  • SECONDARY ID: NCI-2017-00183
  • SECONDARY ID: 2015-1097
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02846623

Conditions

  • Chronic Lymphocytic Leukemia
  • Loss of Chromosome 11q
  • Loss of Chromosome 17p
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Small Lymphocytic Lymphoma
  • Small Lymphocytic Lymphoma
  • TP53 Gene Mutation
  • Untreated Chronic Lymphocytic Leukemia
  • Untreated Small Lymphocytic Lymphoma

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (ibrutinib, obinutuzumab, atezolizumab)
IbrutinibBTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Treatment (ibrutinib, obinutuzumab, atezolizumab)
ObinutuzumabAnti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759Treatment (ibrutinib, obinutuzumab, atezolizumab)

Purpose

This phase II trial studies how well atezolizumab, obinutuzumab, and ibrutinib work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that has come back after a period of improvement, does not respond to treatment, or is high-risk and untreated. Immunotherapy with monoclonal antibodies, such as atezolizumab and obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab, obinutuzumab, and ibrutinib may work better in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the efficacy of atezolizumab in combination with obinutuzumab in patients
      with chronic lymphocytic leukemia (CLL).

      SECONDARY OBJECTIVES:

      I. To determine the safety of atezolizumab combined with obinutuzumab in patients with
      relapsed, refractory or high-risk untreated CLL.

      II. To determine the progression-free survival (PFS) of patients with relapsed, refractory or
      high-risk untreated CLL treated with atezolizumab combined with obinutuzumab.

      III. To determine the overall survival (OS) of this patient population.

      EXPLORATORY OBJECTIVES:

      I. To determine immunological and molecular features, at baseline and/or that change with
      treatment, that correlate with outcomes in patients treated with atezolizumab combined with
      obinutuzumab.

      OUTLINE:

      Patients receive ibrutinib daily on days 1-28, obinutuzumab intravenously (IV) over 4-6 hours
      on days 1, 2, 8, and 15 of course 1 and then on day 1 of courses 2-9, and atezolizumab IV
      over 30-60 minutes on days 1 and 15 of courses 2-9. Treatment repeats every 28 days for up to
      9 courses in the absence of disease or unexpected toxicity.

      After completion of study treatment, patents are followed up monthly for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ibrutinib, obinutuzumab, atezolizumab)ExperimentalPatients receive ibrutinib daily on days 1-28, obinutuzumab IV over 4-6 hours on days 1, 2, 8, and 15 of course 1 and then on day 1 of courses 2-9, and atezolizumab IV over 30-60 minutes on days 1 and 15 of courses 2-9. Treatment repeats every 28 days for up to 9 courses in the absence of disease or unexpected toxicity
  • Atezolizumab
  • Ibrutinib
  • Obinutuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients will have a diagnosis of CLL or small lymphocytic lymphoma (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 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; or
             cohort 3: patients with CLL who have been on ibrutinib for at least 12 months with a
             partial response

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  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 7 days prior to the
             first dose of treatment and must agree to use an effective contraception method during
             the study and for 6 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 6 months following the last dose of study drugs

          -  Patients or their legally authorized representative must provide written informed
             consent

        Exclusion Criteria:

          -  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

          -  Prior treatment for CLL with CTLA-4, PD-1, PD-L1, or CD137 monoclonal antibody (mAb)

          -  Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy,
             experimental therapy within 4 weeks prior to the first dose of the study drugs (except
             ibrutinib for patients in cohort 3); NOTE: for patients on oral targeted therapies
             (such as ibrutinib, idelalisib, IPI-145, ACP-196), a wash-out of 3 days from cycle 1
             day 1 is acceptable

          -  Adverse events from prior anticancer therapy that have not resolved to grade =< 1
             except for alopecia

          -  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 a 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 (defined as >= 2
             consecutive spinal fluid assessments with no evidence of disease)

          -  Active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring
             steroid therapy

          -  Patients with active 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 well as 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) are excluded 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 30 days before cycle 1 day

          -  Patients with organ allografts (such as renal transplant) are excluded

          -  Patients who are on high-dose steroids (doses > 10 mg/day of prednisone or equivalent)
             or immune suppression medications; NOTE: Patients on high-dose steroids (doses > 10
             mg/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

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan

          -  Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis; cirrhosis; fatty liver; and inherited liver disease

          -  Current or chronic hepatitis B or C infection, or known seropositivity for human
             immunodeficiency virus (HIV)

          -  Patient is pregnant or breast-feeding

          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  Patients may not receive other concurrent investigational agent, chemotherapy,
             radiotherapy, or immunotherapy for CLL; NOTE: 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best overall response
Time Frame:Up to 9 courses (252 days)
Safety Issue:
Description:Defined as complete response (CR), complete response with incomplete marrow recovery (iCR), or partial response (PR). Will be estimated along with the 95% credible interval.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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