| Eligibility |
Inclusion Criteria:
- Untreated aggressive B-cell large-B cell lymphoma (non-Hodgkin lymphoma) with adverse
features that may predict sub-optimal response to rituximab-cyclophosphamide,
doxorubicin (hydroxydaunorubicin), vincristine (Oncovin), prednisone (R-CHOP) and in
the opinion of the investigator would be treated with DA-EPOCH-R as standard of care.
Subjects must be planned to receive full course (6 cycles) chemoimmunotherapy as per
clinical standard of care. Composite lymphomas are not excluded provided that the
subject has not receive prior systemic therapy for the indolent component and would
receive DA-EPOCH-R as the standard of care regimen for the aggressive component.
Eligible histologies based on 2016 World Health Organization (WHO) classification
include:
- High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations
- High grade B-cell lymphoma, not otherwise specified (NOS)
- Diffuse large B-cell lymphoma (DLBCL) NOS
- Primary mediastinal B-cell lymphoma
- T-cell/histiocyte-rich large-B-cell lymphoma
- Epstein-Barr virus (EBV) + DLBCL, NOS
- ALK+ large B-cell lymphoma
- B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and
classical Hodgkin lymphoma
- Be willing and able to provide written informed consent for the trial
- Be >= 18 years of age on day of signing informed consent
- Have measurable disease, including at least 1 nodal site measuring 1.5 cm or 1
extranodal site measuring 1.0 cm in longest dimension on computed tomography (CT) or
fluorodeoxyglucose-positron emission tomography (FDG-PET)
- Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)
performance scale (PS)
- Left ventricular ejection fraction (LVEF) >= 50% on cardiac multiple-gated acquisition
(MUGA) scan or cardiac echocardiogram (ECHO)
- Absolute neutrophil count (ANC) >= 1,000/uL except in cases of marrow infiltration by
lymphoma
- Platelets >= 75,000 / mcL except in cases of marrow infiltration by lymphoma or
hypersplenism
- Hemoglobin >= 8 g/dL except in cases of marrow infiltration by lymphoma without red
blood cell (RBC) transfusion within 14 days of first treatment
- Measured or calculated creatinine clearance (Glomerular filtration rate [GFR] can also
be used in place of creatinine or creatinine clearance [CrCl]) >= 40 mL/min.
* Creatinine clearance should be calculated per institutional standard
- Serum total bilirubin =< 1.5 X upper limit of normal (ULN) (Patients with documented
Gilbert disease may be enrolled if total bilirubin =< 3.0 x ULN)
- Direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
ULN OR =< 5 X ULN for subjects with liver involvement
- International Normalized Ratio (INR) or Prothrombin Time (PT) =< 1.5 X ULN unless
subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants, or subject is shown to have an antiphospholipid antibody on workup
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of =< 1% per year during the treatment period and for at least 12 months after the
last dose of study treatment. Women must refrain from donating eggs during this same
period. A woman is considered to be of childbearing potential if she is
post-menarcheal, has not reached a postmenopausal state (=<12 continuous months of
amenorrhea with no identified cause other than menopause), and has not undergone
surgical sterilization (removal of ovaries and/or uterus). The definition of
childbearing potential may be adapted for alignment with local guidelines or
requirements. Examples of contraceptive methods with a failure rate of =<1% per year
include bilateral tubal ligation, male sterilization, hormonal contraceptives that
inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine
devices. The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the patient.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation
methods) and withdrawal are not acceptable methods of contraception
- For women of childbearing potential, a negative serum pregnancy test result during
screening period. Women who are considered not to be of childbearing potential are not
required to have a pregnancy test
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
a condom, and agreement to refrain from donating sperm, as defined below: With female
partners of childbearing potential or pregnant female partners, men must remain
abstinent or use a condom during the treatment period and for at least 6 months after
the last treatment. Men must refrain from donating sperm during this same period. The
reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical trial and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of preventing drug exposure. Male patients
considering preservation of fertility should bank sperm before study treatment
Exclusion Criteria:
- Contraindication to any of the individual components of EPCH-R, including prior
receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to
humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine
products
- Prior systemic treatment for lymphoma with the exception of corticosteroids. Prior
radiotherapy is allowed provided that this site is not used as a measurable site to
assess response.
- Richter's transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma
is not allowed. Transformation from follicular lymphoma is allowed provided that the
subject has not received prior systemic therapy for their lymphoma and the aggressive
component meets one of the criteria listed in inclusion criterion 1
- Diagnosis of Burkitt lymphoma
- Prior organ transplantation
- Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form
of Charcot-Marie-Tooth disease
- Prior systemic therapy for indolent lymphoma
- Prior use of any monoclonal antibody within 3 months of the start of cycle 1; any
investigational therapy within 28 days prior to the start of cycle 1; vaccination with
live vaccines within 28 days prior the start of cycle 1
- Prior therapy for large B-cell lymphoma except for patients who require lymphoma
symptom control during screening may receive steroids in the following manner: Up to
30 mg/day of prednisone or equivalent may be used for lymphoma symptom control during
screening, including prior to finalization of staging (not included as part of
pre-phase treatment) If glucocorticoid treatment is urgently required at higher doses
for lymphoma symptom control prior to the start of study treatment, tumor assessments
must be completed prior to initiation of > 30-100 mg/day of prednisone or equivalent.
Prednisone > 30-100 mg/day or equivalent may be given for a maximum of 7 days as a
pre-phase treatment. If patients exceed the allowed dosing of corticosteroids,
patients may still be eligible for the study provided that baseline imaging is
performed (or repeated) after completion of the course of higher dose of steroids.
Allowed corticosteroid dosing resets from the point of imaging forward and patients
who do not exceed the allowed corticosteroid dosing from the point of imaging until
initiation of study treatment may enroll
- History of other malignancy that could affect compliance with the protocol or
interpretation of results except with permission of the principal investigator. The
following are eligible without a specific waiver:
- Patients with a history of curatively treated basal or squamous cell carcinoma or
melanoma of the skin or in situ carcinoma of the cervix at any time prior to the
study are eligible
- Patients with any malignancy appropriately treated with curative intent and the
malignancy has been in remission without treatment for >= 2 years prior to
enrollment are eligible
- Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below,
Stage 1 or 2) with no requirement for therapy at any time prior to study are
eligible
- Evidence of significant, uncontrolled, concomitant diseases that could affect
compliance with the protocol or interpretation of results, including significant
cardiovascular disease (such as New York Heart Association Class III or IV cardiac
disease, myocardial infarction within the last 6 months, unstable arrhythmias, or
unstable angina) or pulmonary disease (including obstructive pulmonary disease and
history of bronchospasm)
- Recent major surgery (within 4 weeks prior to the start of cycle 1), other than for
diagnosis
- History or presence of an abnormal electrocardiogram (ECG) that is clinically
significant in the investigator's opinion, including complete left bundle branch
block, second- or third-degree heart block, or evidence of prior myocardial infarction
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) which requires systemic treatment. Patients
may proceed with screening during treatment for infection, but systemic treatment must
be completed by cycle 1 day 1
- Positive test results for chronic hepatitis B infection (defined as positive hepatitis
B surface antigen [HBsAg] serology):
* Patients with occult or prior hepatitis B infection (defined as positive total
hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus
(HBV) DNA is undetectable at the time of screening. These patients must be willing to
undergo monthly DNA testing and appropriate antiviral therapy as indicated by
institutional standard
- Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology
testing)
* Patients positive for HCV antibody are eligible only if polymerase chain reaction
(PCR) is negative for HCV ribonucleic acid (RNA)
- History of uncontrolled human immunodeficiency virus (HIV)
* Patients with known diagnosis of HIV must have undetectable viral load and be on
anti-retroviral therapy
- Patients with a history of progressive multifocal leukoencephalopathy
- Pregnancy or lactation or intending to become pregnant during study
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