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

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ClinicalTrials.gov Identifier: NCT03198026
Recruitment Status : Recruiting
First Posted : June 23, 2017
Last Update Posted : March 4, 2019
Sponsor:
Collaborators:
Genentech, Inc.
Pharmacyclics LLC.
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Tracking Information
First Submitted Date  ICMJE June 22, 2017
First Posted Date  ICMJE June 23, 2017
Last Update Posted Date March 4, 2019
Actual Study Start Date  ICMJE February 20, 2018
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2017)
Overall response rate in patients with newly diagnosed indolent lymphoma requiring treatment [ Time Frame: Two years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03198026 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Obinutuzumab and Ibrutinib as Front Line Therapy in Treating Patients With Indolent Non-Hodgkin's Lymphomas
Official Title  ICMJE Phase II, Single Arm, Open Label Multi-center Study of Obinutuzumab and Ibrutinib in the Front Line Treatment of Indolent Non-Hodgkin's Lymphomas
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Hodgkin's Lymphoma
Intervention  ICMJE
  • Drug: Ibrutinib
    Given PO
    Other Names:
    • 2-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-032765
  • Drug: Obinutuzumab
    Given IV
    Other Names:
    • 949142-50-1
    • Anti-CD20 Monoclonal Antibody R7159
    • Gazyva
    • R7159
Study Arms  ICMJE Experimental: Treatment (ibrutinib, obinutuzumab)
Patients 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.
Interventions:
  • Drug: Ibrutinib
  • Drug: Obinutuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 22, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date November 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sameh Gaballa, MD 215 503-0426 sameh.gaballa@jefferson.edu
Contact: Sameh Gaballa, MD 215 503-0426
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03198026
Other Study ID Numbers  ICMJE 17P.176
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
Study Sponsor  ICMJE Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators  ICMJE
  • Genentech, Inc.
  • Pharmacyclics LLC.
Investigators  ICMJE
Principal Investigator: Samah Gaballa, MD Sidney Kimmel Cancer Center at Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP