A Phase II Study of Brentuximab Vedotin Plus Bendamustine for Relapsed/Refractory Follicular Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Bendamustine Hydrochloride
- Conditions
- Recurrent Follicular Lymphoma
- Sponsor
- Joseph Tuscano
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Best overall response rate (ORR)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This phase II trial investigates how well brentuximab vedotin and bendamustine work in treating patients with follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial is being done to determine if the combination of brentuximab vedotin plus bendamustine is safe and to determine the effectiveness of the combination.
Detailed Description
PRIMARY OBJECTIVE: I. Obtain a preliminary estimate of the anti-tumor activity of brentuximab vedotin plus bendamustine hydrochloride (bendamustine) in patients with relapsed/refractory (R/R) CD30+ follicular lymphoma as determined by the complete response rate (CR) and best overall response rate (ORR) as defined per Lugano criteria. SECONDARY OBJECTIVES: To obtain the duration of response (DOR). To obtain the time to response (TTR). To obtain the progression-free survival (PFS) among subjects with relapsed or refractory CD30-positive follicular lymphoma (FL) receiving brentuximab vedotin and bendamustine. To obtain data on overall survival (OS). To evaluate the safety and tolerability. OUTLINE: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and bendamustine IV over 60 minutes on days 1 and 2 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who respond to combination treatment and do not experience excessive toxicity may continue to receive additional single-agent brentuximab vedotin IV over 30 minutes on day 1 (once every 21 days) for up to 10 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days, and then every 3 months for 2 years.
Investigators
Joseph Tuscano
Principal Investigator
University of California, Davis
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed relapsed or refractory follicular CD30+ non-Hodgkin lymphoma (NHL) (included in this category are follicular grade I, II, IIIa). CD30 positivity \> 1% (tumor cells or surrounding peripheral microenvironment)
- •Patients must have measurable disease by computed tomography (CT) or positron emission tomography (PET) scan, with one or more sites of disease \>= 1.5 cm in longest dimension
- •Relapsed or refractory disease after at least 1 prior regimen, defined using the 2014 Lugano classification
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- •Life expectancy of greater than 3 months
- •Leukocytes \>= 2,500/mcL
- •Absolute neutrophil count \>= 1,000/mcL
- •Platelets \>= 50,000/mcL
- •Hemoglobin \>= 8 g/dL
- •Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled)
Exclusion Criteria
- •Patients who have had chemotherapy, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C, steroid treatment for follicular lymphoma is allowed per protocol) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 2 weeks earlier. Specifically, the following therapies are not allowed:
- •Herbal therapy (1 week washout required)
- •Treatment with any other investigational agent within 3 weeks prior to cycle 1, day
- •Prior therapy with bendamustine or a bendamustine-containing regimens with progression within 6 months of receiving treatment
- •Current or prior use of immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 14 days prior to first dose (cycle 1, day 1). The following are exceptions to this criterion:
- •Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10 mg/day of prednisone or equivalent may be enrolled
- •Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
- •The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
- •Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
- •Patients with known uncontrolled central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement
Arms & Interventions
Treatment (brentuximab vedotin, bendamustine)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and bendamustine IV over 60 minutes on days 1 and 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who respond to combination treatment and do not experience excessive toxicity may continue to receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Bendamustine Hydrochloride
Treatment (brentuximab vedotin, bendamustine)
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and bendamustine IV over 60 minutes on days 1 and 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who respond to combination treatment and do not experience excessive toxicity may continue to receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Brentuximab Vedotin
Outcomes
Primary Outcomes
Best overall response rate (ORR)
Time Frame: Up to 2 years
Will be assessed by complete response + partial response per 2014 Lugano criteria and LYRIC criteria.
Complete response (CR) rate
Time Frame: Up to 2 years
Will be assessed per 2014 Lugano criteria and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria. Will be summarized with 95% confidence intervals.
Secondary Outcomes
- Duration of response(From time of initial response assessment demonstrating at least partial response until disease response assessment that demonstrates progressive disease, assessed up to 2 years)
- Time to response(From registration to first disease response assessment that demonstrates at least partial response, assessed up to 2 years)
- Progression-free survival(From registration until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow-up, whichever comes first, assessed up to 2 years)
- Overall survival(From registration to death due to any cause, assessed up to 2 years)