Phase II Venetoclax, Obinutuzumab and Bendamustine in High Tumor Burden Follicular Lymphoma as Front Line Therapy

Phase 2

Completed

Conditions: Follicular Lymphoma
Non-Hodgkin's Lymphoma Follicular
Non-Hodgkin's Lymphoma, Adult High Grade

Interventions: Drug: Induction Venetoclax
Drug: Maintenance Venetoclax

Registration Number: NCT03113422

Lead Sponsor: PrECOG, LLC.

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 56

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Induction Venetoclax	Induction Venetoclax	Cycle 1-6: Obinutuzumab intravenously (IV) and bendamustine IV. Cycle 2-6: Venetoclax (oral)
Maintenance Venetoclax	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.

Primary Outcome Measures

Name	Time	Method
Complete Response (CR) at End of Induction	After 6 cycles (at 28 days/cycle) of induction therapy.	CR assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)

Secondary Outcome Measures

Name	Time	Method
Convert to CR During Maintenance Therapy (From PR in Induction)	Up to 24 cycles which corresponds to 22 months (at 28 days/cycle)	Conversion to CR during Maintenance Therapy assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
Progression-Free Survival (PFS) in the Intent to Treat (ITT) Population.	Up to 24 months	PFS assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
Patient Compliance in Receiving Induction Therapy	Up to 6 cycles (at 28 days/cycle)	Off treatment Reasons
Overall Response Rate (ORR)	After 6 cycles (at 28 days/cycle) of induction therapy	ORR assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)
Number of Participants With Treatment-related GRADE 3+ Adverse Events as Assessed by CTCAE V4.0	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.	Number of participants with abnormal laboratory values and/or adverse events related to treatment of GRADE 3 or higher
Overall Survival (OS) in the ITT Population.	Up to 24 months	OS assessed in accordance with Lymphoma Response Criteria (Lugano Criteria)

Trial Locations

Locations (10): Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Fox Chase
🇺🇸
Philadelphia, Pennsylvania, United States
Gunderson Health System Cancer Center
🇺🇸
La Crosse, Wisconsin, United States
Winship Cancer Institute of Emory University
🇺🇸
Atlanta, Georgia, United States
Sidney Kimmel Comprehensive Cancer Center at John Hopkins
🇺🇸
Baltimore, Maryland, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
University of Virginia
🇺🇸
Charlottesville, Virginia, United States
Rutgers Cancer Institute of NJ
🇺🇸
New Brunswick, New Jersey, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
University of Wisconsin
🇺🇸
Madison, Wisconsin, United States