Trial Title:
A Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma
NCT ID:
NCT05551936
Condition:
Follicular Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Rituximab
Bendamustine Hydrochloride
Conditions: Keywords:
follicular lymphoma
frontline
high tumor burden
EZH2
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Bendamustine
Description:
90 mg/m^2 IV Days 1-2, Cycles 1-3
Arm group label:
Investigational Group
Other name:
Bendeka
Other name:
Treanda
Intervention type:
Drug
Intervention name:
Rituximab
Description:
375 mg/m^2 IV Day 1 Cycles 1-6
Arm group label:
Investigational Group
Other name:
Rituxan
Intervention type:
Drug
Intervention name:
Tazemetostat
Description:
RP2D (400, 600, or 800 mg) orally twice daily Cycles 1-6
Arm group label:
Investigational Group
Other name:
Tazverik
Summary:
This study is planned as a single arm clinical trial of tazemetostat in combination with
bendamustine and rituximab with both a phase I and phase II component. All patients will
receive tazemetostat twice daily on days 1-28 in combination with bendamustine 90 mg/m2
IV on days 1 and 2 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three
cycles. Following this, patients will receive tazemetostat twice daily on days 1-28 and
rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
- Age ≥ 18 years at the time of consent.
- ECOG Performance Status of 0-2 within 10 days prior to registration.
- Low grade follicular lymphoma (grade 1-2 or 3A by WHO-HAEM4R and/or cFL by
WHO-HAEM5). Specifically, grade 3B or FLBL will not be allowed. Must not have
evidence of transformed lymphoma at the time of study enrollment.
- Stage II, III, or IV by Ann Arbor staging system.
- Meet the definition of high tumor burden follicular lymphoma as defined by Groupe
d'Etude des Lymphomes Follicularies (GELF) Criteria or be defined as high risk by
the follicular lymphoma international prognostic index (FLIPI) 1 or FLIPI 2.
--GELF Criteria (Must meet ≥ 1 of the following)
- Any nodal or extranodal mass ≥ 7 cm in diameter
- Involvement of ≥ 3 nodal sites ≥ 3 cm
- Systemic or B symptoms
- Presence of serous effusion
- Splenic enlargement
- Risk of compression syndrome (epidural, ureteral, etc)
- Leukemic phase of disease
- Cytopenia deemed due to disease involvement (hemoglobin < 10, granulocyte count
< 1.5×10^9/L, or platelet count < 100×10^9/L)
- In addition to meeting GELF criteria, must have at least one FDG-avid site on PET
that measures 1.5 cm in at least one dimension of a nodal site or 1cm in at least
one dimension for extranodal sites.
- Received no prior therapy except local radiation therapy (field did not exceed 2
adjacent nodal regions), single agent rituximab (limited to 4 doses), or steroids
for symptom control in the 28 days preceding trial enrollment.
- Must have prior EZH2 testing already performed or have tissue available to perform
retrospective EZH2 testing. If prior EZH2 results are not available, tissue must be
submitted. Tissue block is preferred but unstained slides are also acceptable.
Patients who have insufficient or suboptimal tissue must be willing to have a biopsy
performed prior to starting study drugs. See Correlative Lab Manual for details.
- Demonstrate adequate organ function as defined below; all screening labs to be
obtained within 28 days prior to registration.
- Hematological
- Platelets ≥ 50 K/dL
- Absolute Neutrophil Count (ANC) ≥ 1000 K/mm3
- Hemoglobin (Hgb) ≥ 8 g/dL
- Renal
- Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault
formula
- or Serum creatinine < 2 mg/dL
- Hepatic
- Bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 3 × ULN
- Alanine aminotransferase (ALT) ≤ 3 × ULN
- Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT)
Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN
- Females of childbearing potential with a male partner able to father a child must
have a negative serum or urine pregnancy test within 7 days prior to registration.
See the protocol for definition of childbearing potential.
- Females of childbearing potential must be willing to abstain from vaginal
intercourse or use an effective method(s) of contraception from the time of informed
consent, during the study and for 6 months after the last dose of study drug(s).
Males able to father a child must be willing to abstain from vaginal intercourse or
to use an effective method(s) of contraception from initiation of treatment, during
the study and for 3 months after the last dose of study drug(s). See the protocol.
- As determined by the enrolling physician or protocol designee, ability of the
subject to understand and comply with study procedures for the entire length of the
study.
Exclusion Criteria:
- Active infection requiring systemic therapy with 4 weeks of study drug
administration.
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while
the mother is being treated on study).
- Concurrent malignancy or malignancy within the last 3 years (except for ductal
breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring
treatment, and cervical carcinoma in situ) whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen are not eligible for this trial.
- Active central nervous system (CNS) metastases or leptomeningeal disease. NOTE:
Subjects who are symptomatic and have not undergone prior brain imaging must undergo
a head computed tomography (CT) scan or brain MRI within 28 days prior to
registration to exclude brain metastases.
- Treatment with any investigational drug within 4 weeks prior to registration.
- Subjects who require chronic use of moderate or strong CYP3A4/5 inhibitors or
inducers within 28 days prior to registration.
- Clinically significant acute infection requiring systemic antibacterial, antifungal,
or antiviral therapy.
- Known Uncontrolled Human Immunodeficiency Virus infection. Testing not required.
NOTE: If a subject is known to have HIV/AIDS, then they will be allowed on study
with adequate antiviral therapy, no detectable viral load, and stable on antiviral
treatment for ≥ 4 weeks prior to first dose of study drug(s).
- Known hepatitis C infection. Testing not required. NOTE: If hepatitis C antibody
test is known positive, patients are excluded unless a hepatitis C virus ribonucleic
acid (HCV RNA) is negative.
- Must be tested for hepatitis B within 28 days of registration: including hepatitis B
surface antigen, hepatitis B surface antibody, hepatitis B core antibody. A positive
hepatitis B core antibody should be followed by hepatitis B DNA PCR testing to
confirm or rule out active infection. Patients with hepatitis B surface antigen
and/or detectable hepatitis B DNA PCR are not allowed on study. Patients with a
positive hepatitis B core antibody but negative hepatitis B surface antigen and
hepatitis B DNA PCR will be allowed on study, but hepatitis B prophylactic treatment
should be strongly considered.
- Clinically significant cardiovascular disease or cardiac insufficiency (New York
Heart Association classes III-IV), cardiomyopathy, preexisting clinically
significant arrhythmia, acute myocardial infarction within 3 months of enrollment,
angina pectoris within 3 months of enrollment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Phone:
312-695-1310
Email:
cancer@northwestern.edu
Investigator:
Last name:
Reem Karmali, MD
Email:
Principal Investigator
Facility:
Name:
University of Illinois Cancer Center
Address:
City:
Chicago
Zip:
60612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kimberly Saulsberry
Email:
ksauls2@uic.edu
Investigator:
Last name:
Carlos Galvez, MD
Email:
Principal Investigator
Facility:
Name:
Rutgers Cancer Institute of New Jersey
Address:
City:
New Brunswick
Zip:
08903
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kellie Harper
Phone:
732-675-4331
Email:
kh920@cinj.rutgers.edu
Investigator:
Last name:
Andrew Evens, DO
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Misty Fleming
Email:
misty.fleming@osumc.edu
Investigator:
Last name:
Naren Epperla, MD
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center
Address:
City:
Madison
Zip:
53705
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jennifer Burken, MS
Email:
burkenbrett@wisc.edu
Investigator:
Last name:
Vaishalee Kenkre, MD
Email:
Principal Investigator
Start date:
January 26, 2023
Completion date:
May 2027
Lead sponsor:
Agency:
Vaishalee Kenkre
Agency class:
Other
Collaborator:
Agency:
Epizyme, Inc.
Agency class:
Industry
Collaborator:
Agency:
University of Wisconsin, Madison
Agency class:
Other
Source:
Big Ten Cancer Research Consortium
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05551936
