Phase II Venetoclax, Obinutuzumab and Bendamustine in High Tumor Burden Follicular Lymphoma as Front Line Therapy (PrE0403)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03113422|
Recruitment Status : Active, not recruiting
First Posted : April 13, 2017
Last Update Posted : November 13, 2020
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).
|Condition or disease||Intervention/treatment||Phase|
|Follicular Lymphoma Non-Hodgkin's Lymphoma Follicular Non-Hodgkin's Lymphoma, Adult High Grade||Drug: Induction Venetoclax Drug: Maintenance Venetoclax||Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||56 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Venetoclax (ABT-199/GDC-0199) in Combination With Obinutuzumab and Bendamustine in Patients With High Tumor Burden Follicular Lymphoma as Front Line Therapy|
|Actual Study Start Date :||December 27, 2017|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||March 2024|
Experimental: Induction Venetoclax
Cycle 1-6: Obinutuzumab intravenously (IV) and bendamustine IV. Cycle 2-6: Venetoclax (oral)
Drug: Induction Venetoclax
1 cycle = 28 days.
Experimental: Maintenance Venetoclax
Patients with stable or improved disease will receive venetoclax by mouth daily for 24 cycles (1 cycle=1 month) and obinutuzumab IV every 2 months for 12 cycles. Patients with no evidence of disease will receive obinutuzumab IV every 2 months for 12 cycles.
Drug: Maintenance Venetoclax
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.
- Complete Response (CR) at End of Induction [ Time Frame: 45 months ]CR assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)
- Overall Response Rate (ORR) [ Time Frame: 75 months ]ORR assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)
- Convert to CR during Maintenance Therapy [ Time Frame: 72 months ]Conversion to CR during Maintenance Therapy assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)
- Progression-Free Survival (PFS) in the intent to treat (ITT) population. [ Time Frame: 75 months ]PFS assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)
- Overall Survival (OS) in the ITT population. [ Time Frame: 75 months ]OS assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 75 months ]Number of participants with abnormal laboratory values and/or adverse events related to treatment
- Patient compliance in receiving induction and maintenance therapy [ Time Frame: 75 months ]Medication diary to tabulate missing doses of venetoclax per patient and record number of doses received for obinutuzumab and bendamustine per patient.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03113422
|United States, Georgia|
|Winship Cancer Institute of Emory University|
|Atlanta, Georgia, United States, 30322|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at John Hopkins|
|Baltimore, Maryland, United States, 21205|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Rutgers Cancer Institute of NJ|
|New Brunswick, New Jersey, United States, 08903|
|United States, Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19111|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Virginia|
|University of Virginia|
|Charlottesville, Virginia, United States, 22908|
|United States, Wisconsin|
|Gunderson Health System Cancer Center|
|La Crosse, Wisconsin, United States, 54601|
|University of Wisconsin|
|Madison, Wisconsin, United States, 53792|
|Study Chair:||Nishitha M Reddy, MD||Vanderbilt-Ingram Cancer Center|