Patients with high tumor burden, low grade follicular lymphoma that has never been treated, will receive venetoclax in combination with obinutuzumab and bendamustine. Venetoclax is an oral Bcl-2 family protein inhibitor. It targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with follicular lymphoma. Venetoclax may help to slow down the growth of cancer or may cause cancer cells to die. The purpose of this study is to see whether adding venetoclax to obinutuzumab and bendamustine improves the response (the tumor shrinks or disappears) in patients with follicular lymphoma. As of 9/5/2018, a higher than expected incidence of tumor lysis syndrome (TLS) was experienced among patients receiving venetoclax, obinutuzumab and bendamustine on Cycle 1, Day 1 of treatment. TLS is caused by the fast breakdown of cancer cells. These patients developed an increase in some of their blood tests (uric acid, phosphorus, potassium and/or creatinine). They received a medication called rasburicase and continued with treatment. It is unclear if the TLS was due to the venetoclax or the standard treatment of obinutuzumab and bendamustine. For the remaining patients, venetoclax will start on Cycle 2, Day 1 (previously Cycle 1, Day 1). As of 9/16/2021, additional maintenance therapy has been suspended for those patients who remain on study. These patients will not receive any further treatment and will move on to the two year survival follow-up.
Follicular lymphoma (FL) is the most common low grade lymphoma comprising 70% of low-grade non-Hodgkin's lymphoma (NHL) and 22% of all cases of NHL. The survival rates for patients with indolent NHL remained unchanged from the 1950s through the early 1990s, but recent evidence suggests that outcomes continue to improve. High-risk patients with FL, defined as having advanced stage and high tumor burden have significantly shorter progression free survival despite significant advances. This is an open-label phase II study of venetoclax in combination with obinutuzumab and bendamustine. Patients will receive induction therapy with obinutuzumab and bendamustine for six cycles (1 cycle = 28 days). Venetoclax will start with 2nd cycle of induction therapy (previously started with cycle 1). There will be a formal, detailed toxicity evaluation after 21 patients complete 3 cycles of treatment. Patients who achieve partial response or stable disease will receive therapy with obinutuzumab every 2 months for 12 cycles and venetoclax every month for 24 cycles. Patients who achieve a complete response will receive obinutuzumab every 2 months for 12 cycles. Patients with progressive disease will not continue onto the maintenance arm. Tumor assessments will be performed approximately every 12 weeks during induction and every 6 months during maintenance therapy. Mandatory pre-treatment tumor tissue sample (i.e., obtained during a previous procedure or biopsy) will be required for research (if sufficient tissue is available). Optional tumor biopsy samples obtained during treatment or post-treatment will also be requested for research.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
1 cycle = 28 days. * Cycle 1-6: Obinutuzumab IV. Cycle 1, Day 1 obinutuzumab 100 mg and Cycle 1, Day 2 obinutuzumab 900 mg for total dose of 1000 mg. On Cycle 1, Day 8 and Day 15 obinutuzumab 1000 mg. Starting with Cycle 2, obinutuzumab 1000 mg on Day 1 only of each cycle. * Cycle 1-6: Bendamustine 90 mg/m² IV on Days 1 and 2 of each cycle over 15 minutes after obinutuzumab. * Cycle 2-6: Venetoclax 800 mg by mouth daily on Days 1-10 administered before obinutuzumab and/or bendamustine.
Patients whose disease is the same or improved will receive venetoclax 800 mg by mouth daily for 24 cycles (1 cycle=1 month) and obinutuzumab 1000 mg IV every 2 months for 12 cycles. Patients with no evidence of disease will receive obinutuzumab 1000 mg IV every 2 months for 12 cycles.
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Rutgers Cancer Institute of NJ
New Brunswick, New Jersey, United States
Fox Chase
Philadelphia, Pennsylvania, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
University of Virginia
Charlottesville, Virginia, United States
Gunderson Health System Cancer Center
La Crosse, Wisconsin, United States
University of Wisconsin
Madison, Wisconsin, United States
Complete Response (CR) at End of Induction
CR assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
Time frame: After 6 cycles (at 28 days/cycle) of induction therapy.
Overall Response Rate (ORR)
ORR assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
Time frame: After 6 cycles (at 28 days/cycle) of induction therapy
Convert to CR During Maintenance Therapy (From PR in Induction)
Conversion to CR during Maintenance Therapy assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
Time frame: Up to 24 cycles which corresponds to 22 months (at 28 days/cycle)
Progression-Free Survival (PFS) in the Intent to Treat (ITT) Population.
PFS assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
Time frame: Up to 24 months
Overall Survival (OS) in the ITT Population.
OS assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
Time frame: Up to 24 months
Number of Participants With Treatment-related GRADE 3+ Adverse Events as Assessed by CTCAE V4.0
Number of participants with abnormal laboratory values and/or adverse events related to treatment of GRADE 3 or higher
Time frame: Adverse events were captured through 6 cycles of therapy (at 28 days/cycle) and for 30 days after the last dose, for a total assessment period of approximately 7 months.
Patient Compliance in Receiving Induction Therapy
Off treatment Reasons
Time frame: Up to 6 cycles (at 28 days/cycle)
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