Clinical Trials /

Obinutuzumab and Ibrutinib as Front Line Therapy in Treating Patients With Indolent Non-Hodgkin's Lymphomas

NCT03198026

Description:

This phase II trial studies how well obinutuzumab and ibrutinib work as front line therapy in treating patients with indolent non-Hodgkin's lymphoma. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obinutuzumab and ibrutinib may work better in treating patients with non-Hodgkin's lymphomas.

Related Conditions:
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Obinutuzumab and Ibrutinib as Front Line Therapy in Treating Patients With Indolent Non-Hodgkin's Lymphomas
  • Official Title: Phase II, Single Arm, Open Label Multi-center Study of Obinutuzumab and Ibrutinib in the Front Line Treatment of Indolent Non-Hodgkin's Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 17P.176
  • NCT ID: NCT03198026

Conditions

  • Non-Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
Ibrutinib2-Propen-1-one, 1-((3R)-3-(4-amino-3-(4-phenoxyphenyl)-1h-pyrazolo(3,4-d)pyrimidin-1-yl)-1-piperidinyl)-, BTK Inhibitor PCI-32765, CRA-032765Treatment (ibrutinib, obinutuzumab)
Obinutuzumab949142-50-1, Anti-CD20 Monoclonal Antibody R7159, Gazyva, R7159Treatment (ibrutinib, obinutuzumab)

Purpose

This phase II trial studies how well obinutuzumab and ibrutinib work as front line therapy in treating patients with indolent non-Hodgkin's lymphoma. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obinutuzumab and ibrutinib may work better in treating patients with non-Hodgkin's lymphomas.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the efficacy of the combination of ibrutinib and obinutuzumab in chemotherapy
      naive patients with indolent lymphomas.

      SECONDARY OBJECTIVES:

      I. To assess progression free survival rates and overall survival rates in indolent
      lymphomas.

      II. To assess safety and tolerability of the combination. III. To evaluate response using
      positron emission tomography (PET) and correlate PET negativity with durability of response.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ibrutinib, obinutuzumab)ExperimentalPatients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 months after course 6, patients with stable disease will continue to receive obinutuzumab every 2 months for a total of 12 doses.
  • Ibrutinib
  • Obinutuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  • Previously untreated, histologically confirmed indolent non-Hodgkin's lymphoma as
             follows:

               -  Follicular lymphoma (World Health Organization [WHO] classification grade 1, 2,
                  or 3a)

               -  Marginal zone lymphoma including:

                    -  Nodal and splenic marginal zone lymphoma (MZL) who have an indication for
                       systemic therapy

                    -  Extranodal MZL:

                         -  Nongastric/noncutaneous MZL requiring systemic therapy

                         -  Cutaneous MZL will be eligible only if they have pathologically
                            confirmed extra-cutaneous disease

                         -  Gastric MZL only if stage IIIE/IV defined as lymph node involvement on
                            both sides of the diaphragm or with disseminated extranodal disease
                            such as bone marrow or additional extra nodal sites

                              -  Pathological diagnosis should be obtained by incisional or
                                 excisional tissue biopsy; core biopsy is permissible if obtaining
                                 an incisional or excisional is not possible and if the grade can
                                 be assessed on the core biopsy. A core biopsy can also be used if
                                 deemed in the best interest of the patient in the opinion of the
                                 investigator

                              -  Patients must have stage II-IV disease

                              -  All patients should have measurable disease; measurable disease is
                                 defined as a lymph node or tumor mass that is >= 1.5 cm in at
                                 least one dimension by computed tomography (CT) or the CT portion
                                 of the PET/CT

                              -  Documentation of CD20+ status

                              -  Patients must have an indication for therapy per standard modified
                                 Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
                                 including:

               -  Symptoms attributable to lymphoma, threatened end-organ function, cytopenia
                  secondary to lymphoma, bulky disease (defined as: single mass > 7 cm in diameter,
                  or 3 or more masses > 3 cm in diameter), splenomegaly, and steady progression
                  over at least 6 months

                    -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

                    -  Patients must be able to swallow whole pills

                    -  Ability and willingness to comply with the requirements of the study
                       protocol. When it is determined by the study investigator that a potential
                       research participant is cognitively impaired, a surrogate consent from a
                       caregiver or legally-authorized representative will be obtained. Caregiver
                       or legally-authorized representative will ensure that they comply with the
                       protocol in order for the subject to be considered eligible.

                    -  Female subjects who are of non-reproductive potential (i.e., post-menopausal
                       by history - no menses for >= 1 year; OR history of hysterectomy; OR history
                       of bilateral tubal ligation; OR history of bilateral oophorectomy); female
                       subjects of childbearing potential must have a negative urine/serum
                       pregnancy test upon study entry

                    -  Male and female subjects who agree to use both a highly effective method of
                       birth control (e.g., implants, injectables, combined oral contraceptives,
                       some intrauterine devices [IUDs], complete abstinence , or sterilized
                       partner) and a barrier method (e.g., condoms, vaginal ring, sponge, etc)
                       during the period of therapy; female patients of reproductive potential who
                       are not surgically sterile must practice adequate birth control for a
                       minimum of twelve months post-treatment; male patients who are not
                       surgically sterile must practice adequate birth control for a minimum of
                       three months post-treatment

                    -  Absolute neutrophil count > 1.5 x 10^9 cells/mm^3

                    -  Platelet count > 50,000 cells/mm^3 (50 x 10^9/L)

                    -  Hemoglobin > 9.0 g/dL

                    -  Serum aspartate transaminase or alanine transaminase =< 3.0 x upper limit of
                       normal (ULN)

                    -  Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and
                       activated partial thromboplastin time (aPTT) < 1.5 x ULN (unless
                       abnormalities are unrelated to coagulopathy or bleeding disorder)

                    -  Estimated creatinine clearance >= 30 ml/min (calculated according using
                       Cockcroft-Gault formula)

                    -  Bilirubin =< 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome
                       or of non-hepatic origin)

                    -  Patients with Child Pugh B or C liver failure will be excluded

        Exclusion Criteria:

          -  Prior history of malignancies unless the patient has been disease free for >= 5 years;
             exceptions include basal cell carcinoma or squamous cell carcinoma of the skin;
             carcinoma in situ of cervix; carcinoma in situ of breast, localized prostate cancer,
             or superficial bladder cancer that has undergone curative therapy

          -  Prior therapy for lymphoma including chemotherapy or immunotherapy including
             ibrutinib/anti-CD20 agents; patient may have received corticosteroids, but should be
             off them 2 weeks prior to study entry; known prior significant hypersensitivity to
             obinutuzumab (not including infusion reactions) or ibrutinib

          -  Patients with evidence of large B cell transformation (transformed disease) are not
             eligible.

          -  Known central nervous system (CNS) involvement by lymphoma

          -  Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)

          -  Concomitant use of warfarin or other vitamin K antagonists

          -  Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor

          -  Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding
             fungal infections of nail beds) or any major episode of infection requiring treatment
             with IV antibiotics or hospitalization (related to the completion of the course of
             antibiotics) within 4 weeks before the start of cycle 1

          -  Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus
             1 (HTLV-1) seropositive status

          -  Viral hepatitis:

               -  Patients with active hepatitis B defined by hepatitis B surface antigen
                  positivity or core antibody positivity in the presence of detectable serum
                  hepatitis B deoxyribonucleic acid (DNA) viremia are not eligible for this study

               -  Patients with a positive hepatitis B core antibody but with negative hepatitis B
                  DNA maybe considered for participation, but must agree to receive appropriate
                  anti-hepatitis B viral therapy suppression therapy while on obinutuzumab and have
                  hepatitis B DNA monitored every 4 weeks with real-time polymerase chain reaction
                  (PCR) by the treating physician; these patients should be referred to a
                  hepatologist or gastroenterologist for appropriate monitoring and management

               -  Hepatitis C: patients with positive hepatitis C serology unless hepatitis C virus
                  (HCV) ribonucleic acid (RNA) is confirmed negative by PCR

          -  Vaccination with a live vaccine a minimum of 28 days prior to the start of treatment

          -  Patient is receiving other investigational drugs

          -  Prior chemotherapy for any other cancer within the last 2 years

          -  Patients should not have active or uncontrolled autoimmune hemolytic anemia or immune
             thrombocytopenia

          -  Patients should not have transfusion-dependent thrombocytopenia or bleeding disorders

          -  Patients should not have an autoimmune disorder that requires active immunosuppression

          -  Patients should not have a history of uncontrolled seizures

          -  Currently active, clinically significant cardiovascular disease, such as uncontrolled
             arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart
             Association functional classification; or a history of myocardial infarction, unstable
             angina, or acute coronary syndrome within 6 months prior to enrollment on the study

          -  Patients should not have a stroke or intracranial hemorrhage within last 6 months

          -  Prior surgery: patients may not have had major surgery within 28 days of enrollment,
             or minor surgery within 7 days of enrollment; examples of minor surgery include dental
             surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint;
             the decision about whether a surgery is major or minor can be made at the discretion
             of the treating physician

          -  Any life-threatening illness, medical condition, or organ system dysfunction that, in
             the investigator's opinion, could compromise the subject's safety or put the study
             outcomes at undue risk

          -  Pregnant and nursing: female patients must have a negative serum pregnancy test within
             72 hours prior to initiating protocol therapy and be practicing an effective form of
             contraception during protocol therapy and for at least 4 weeks following completion of
             protocol therapy

          -  Currently active, clinically significant hepatic impairment Child-Pugh class B or C
             according to the Child Pugh classification
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate in patients with newly diagnosed indolent lymphoma requiring treatment
Time Frame:Two years
Safety Issue:
Description:Response will be assessed by the revised Lugano. Will compute estimates of response, along with corresponding confidence intervals, using appropriate exact methods that take into account the 2-stage design.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

Last Updated