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

  • STATUS
    Recruiting
  • days left to enroll
    5
  • participants needed
    30
  • sponsor
    Sidney Kimmel Cancer Center at Thomas Jefferson University
Updated on 23 March 2021
ct scan
platelet count
cancer
hodgkin's disease
monoclonal antibodies
measurable disease
cytopenia
neutrophil count
follicular lymphoma
marginal zone lymphoma
ibrutinib
obinutuzumab
indolent lymphoma

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.

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.

Details
Condition Follicular Lymphoma, Follicular Lymphoma, Lymphoma, Non-Hodgkin's Lymphoma, Lymphoma, Non-Hodgkin's Lymphoma, Grade 3a Follicular Lymphoma, Ann Arbor Stage II Follicular Lymphoma, Ann Arbor Stage III Follicular Lymphoma, Ann Arbor Stage IV Follicular Lymphoma, non-hodgkin's lymphoma (nhl), Ann Arbor Stage II Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Ann Arbor Stage II Nodal Marginal Zone Lymphoma, Ann Abor Stage III B-Cell Non-Hodgkin Lymphoma, Ann Arbor Stage III Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Ann Arbor Stage III Nodal Marginal Zone Lymphoma, Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma, Ann Arbor Stage IV Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Ann Arbor Stage IV Nodal Marginal Zone Lymphoma, Indolent Non-hodgkin Lymphoma, Stage II Splenic Marginal Zone Lymphoma, Stage III Splenic Marginal Zone Lymphoma, Stage IV Splenic Marginal Zone Lymphoma, Ann Arbor Stage II Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Ann Abor Stage III B-Cell Non-Hodgkin Lymphoma, Ann Arbor Stage III Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma, Ann Arbor Stage IV Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Indolent Non-hodgkin Lymphoma
Treatment Ibrutinib, Obinutuzumab
Clinical Study IdentifierNCT03198026
SponsorSidney Kimmel Cancer Center at Thomas Jefferson University
Last Modified on23 March 2021

Eligibility

Yes No Not Sure

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note