Overview

Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma

Status:
Active, not recruiting
Trial end date:
2030-05-08
Target enrollment:
0
Participant gender:
All
Summary
RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bendamustine hydrochloride and rituximab together alone is more effective than giving bendamustine hydrochloride and rituximab together with bortezomib or lenalidomide in treating follicular lymphoma. PURPOSE: This randomized phase II trial is studying giving bendamustine hydrochloride and rituximab together with or without bortezomib followed by rituximab with or without lenalidomide to see how well they work in treating patients with high-risk stage II, stage III, or stage IV follicular lymphoma.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Eastern Cooperative Oncology Group
ECOG-ACRIN Cancer Research Group
Collaborator:
National Cancer Institute (NCI)
Treatments:
Bendamustine Hydrochloride
Bortezomib
Lenalidomide
Rituximab
Thalidomide
Criteria
Inclusion Criteria (Induction):

- Histologically confirmed (biopsy-proven) diagnosis of follicular B-cell non-Hodgkin
lymphoma with no evidence of transformation to large cell histology

- Patients having both diffuse and follicular architectural elements are eligible
if the histology is predominantly follicular (i.e., ≥ 50% of the cross-sectional
area) and there is no evidence of transformation to a large cell histology

- Diagnostic confirmation (i.e., core needle or excisional lymph node biopsy)
required if the interval since tissue diagnosis of low-grade malignant lymphoma
is > 24 months

- Bone marrow biopsy alone not acceptable

- Stage II, III, or IV AND grade 1, 2, or 3a disease

- Must meet criteria for High Tumor Burden (higher risk) as defined by either the Groupe
D'Etude des Lymphomes Follicularies (GELF) criteria OR the follicular lymphoma
international prognostic index (FLIPI) as defined below:

- Patient must meet ≥ 1 of the following GELF criteria:

- Nodal or extranodal mass ≥ 7 cm

- At least 3 nodal masses > 3.0 cm in diameter

- Systemic symptoms due to lymphoma or B symptoms

- Splenomegaly with spleen > 16 cm by CT scan

- Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal)
or pleural or peritoneal serous effusion due to lymphoma (irrespective of
cell content)

- Leukemic presentation (≥ 5.0 x 10^9/L malignant circulating follicular
cells)

- Cytopenias (polymorphonuclear leukocytes < 1.0 X 10^9/L, hemoglobin < 10
g/dL, and/or platelets < 100 x 10^9/L)

- Patient must have a FLIPI-1 score of 3, 4, or 5 (1 point per criterion below):

- Age ≥ 60 years

- Stage III-IV disease

- Hemoglobin level < 12 g/dL

- > 4 nodal areas

- Serum lactate dehydrogenase (LDH) level above normal

- At least 1 objective measurable disease parameter

- Baseline measurements and evaluations (PET and CT) obtained within 6 weeks of
randomization

- Measurable disease in the liver is required if the liver is the only site of
lymphoma

- HIV-positive patients must meet all of the following criteria:

- HIV is sensitive to antiretroviral therapy

- Must be willing to take effective antiretroviral therapy if indicated

- No history of CD4 < 300 cells/mm³ prior to or at the time of lymphoma diagnosis

- No history of AIDS-defining conditions

- If on antiretroviral therapy, must not be taking zidovudine or stavudine

- Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP)
during therapy and ≥ 2 months following completion of study therapy or until the
CD4 cells recover to over 250 cells/mm³

- ECOG performance status 0-2

- Absolute neutrophil count (ANC) ≥ 1,500/mm³ (includes neutrophils and bands)

- Platelet count ≥ 100,000/mm³

- Creatinine ≤ 2.0 mg/dL

- Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 5 x upper limit of
normal (ULN)

- Alkaline phosphatase ≤ 5 x ULN

- Total bilirubin ≤ 1.5 x ULN (patients with known Gilbert disease should contact the
study PI)

- Negative pregnancy test

- Fertile patients must use 2 effective methods (1 highly effective and 1 additional
effective method) of contraception ≥ 28 days before, during, and for ≥ 28 days after
completing study treatment

- Must register into the mandatory RevAssist® program and be willing and able to comply
with the requirements of RevAssist® (for patients randomized to arm C and proceed onto
arm F)

Exclusion Criteria (Induction):

- Prior chemotherapy, radiotherapy, or immunotherapy for lymphoma

- Prednisone or other corticosteroids used for non-lymphomatous conditions will not
be considered as prior chemotherapy

- A prior/recent short course (< 2 weeks) of steroids for symptom relief of
lymphoma-related symptoms is allowed

- Recent history of malignancy except for adequately treated basal cell or squamous cell
skin cancer, in situ cervical cancer, or other cancer for which the patient has been
disease-free for ≥ 2 years

- Pregnant or nursing

- Active, uncontrolled infections (afebrile for > 48 hours off antibiotics)

- ≥ grade 2 neuropathy

- Myocardial infarction within the past 6 months

- NYHA class III-IV heart failure, uncontrolled angina, severe uncontrolled ventricular
arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction
system abnormalities

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study

- Known hypersensitivity to boron or mannitol

- Chronic carriers of hepatitis B virus (HBV) with positive hepatitis surface antigen
(HBsAg +)

Inclusion Criteria (Continuation):

- Patient must have improved their response or have had no interval change in their
tumor measurements with restaging from Induction cycle 3 to 6 as determined at Cycle 6
restaging.

- Adequate organ function

- ECOG performance status 0-2

- Patients with a prior history of HBV infection, but immune, with only IgG hepatitis
core antibody positive (HBcAb+), must receive antiviral prophylaxis (e.g., lamivudine
100 mg po daily) for ≥ 1 week prior to course 1 and throughout induction and
continuation therapy and for ≥ 12 months after the last rituximab dose

- Additional requirements for Arm C induction patients registering to arm F:

- Patients must be willing to take deep vein thrombosis (DVT) prophylaxis. Subjects
with a history of a thrombotic vascular event will be required to have full
anticoagulation, therapeutic doses of low molecular weight heparin or warfarin to
maintain an INR between 2.0 - 3.0, or any other accepted full anticoagulation
regimen (e.g. direct thrombin inhibitors or Factor Xa inhibitors) with
appropriate monitoring for that agent. Subjects without a history of a
thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for
DVT prophylaxis. Subjects who are unable to tolerate aspirin should receive low
molecular weight heparin therapy or warfarin treatment or another accepted full
anticoagulation regimen.

- Females of childbearing potential (FCBP) must agree to use two reliable forms of
contraception simultaneously or to practice complete abstinence from heterosexual
intercourse during the following time periods related to this study/lenalidomide:
1) for at least 28 days before starting lenalidomide; 2) while participating in
the study; and 3) for at least 28 days after discontinuation/stopping
lenalidomide. The two methods of reliable contraception must include one highly
effective method (i.e. intrauterine device (IUD), hormonal [birth control pills,
injections, or implants], tubal ligation, partner's vasectomy) and one additional
effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP
must be referred to a qualified provider of contraceptive methods if needed.

- Patient must agree to abstain from donating blood during study participation and
for at least 28 days after discontinuation from protocol treatment.

- All males, regardless of whether they have undergone a successful vasectomy, must
agree to use a latex condom during sexual contact with a female of childbearing
potential, or to practice complete abstinence from heterosexual intercourse with
any female of childbearing potential during the cycles of continuation therapy of
which lenalidomide are taken and for at least 28 days after
discontinuation/stopping lenalidomide. Patient must agree to abstain from
donating blood, semen, or sperm during study participation and for at least 28
days after discontinuation from protocol treatment.

- Must register into the mandatory RevAssist® program and be willing and able to
comply with the requirements of RevAssist®

Exclusion Criteria (Continuation):

- Active, uncontrolled infections (afebrile for > 48 hours off antibiotics)

- ≥ grade 2 neuropathy

- Additional requirements for Arm C induction patients registering to arm F:

- Not pregnant or breast-feeding