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Testing CC-486 (Oral Azacitidine) Plus the Standard Drug Therapy in Patients 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma
Recruiting
I'm InterestedTrial ID: NCT04799275
Purpose
This phase II/III trial compares the side effects and activity of oral azacitidine in
combination with the standard drug therapy (reduced dose rituximab-cyclophosphamide,
doxorubicin, vincristine, and prednisone [R-miniCHOP]) versus R-miniCHOP alone in treating
patients 75 years or older with newly diagnosed diffuse large B cell lymphoma. R-miniCHOP
includes a monoclonal antibody (a type of protein), called rituximab, which attaches to the
lymphoma cells and may help the immune system kill these cells. R-miniCHOP also includes
prednisone which is an anti-inflammatory medication and a combination of 3 chemotherapy
drugs, cyclophosphamide, doxorubicin, and vincristine. These 3 chemotherapy drugs, as well as
oral azacitidine, 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.
Combining oral azacitidine with R-miniCHOP may shrink the cancer or extend the time without
disease symptoms coming back or extend patient's survival when compared to R-miniCHOP alone.
Official Title
A Phase II/III Randomized Study of R-MiniCHOP With or Without CC-486 (Oral Azacitidine) in Participants Age 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma, Grade IIIB Follicular Lymphoma, Transformed Lymphoma, and High-Grade B-Cell Lymphomas With MYC AND BCL2 and/or BCL6 Rearrangements
Stanford Investigator(s)
Ranjana Advani
Saul A. Rosenberg, MD, Professor of Lymphoma
Eligibility
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed diffuse large B-cell
lymphoma (DLBCL), Ann Arbor Stage IIX (bulky), III or IV. Participants with DLBCL
transformed from follicular lymphoma (FL) or marginal zone lymphoma (MZL, including
mucosa-associated lymphoid tissue [MALT] lymphomas), lymphoplasmacytic lymphoma (LPL),
or nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL) are eligible. Participants
with Grade IIIB follicular lymphoma (FL) or high-grade B-cell lymphomas with MYC and
BCL2 and/or BCL6 rearrangements are also eligible. Participants with DLBCL that arose
from prior CLL (Richter's transformation) are not eligible.
- As defined by the World Health Organization (WHO), eligible lymphoma subtypes include
the following:
- DLBCL, not otherwise specified (NOS)
- DLBCL, germinal-center B-cell type (GCB)
- DLBCL, activated B-cell type (ABC)
- T-cell histiocyte-rich B-cell lymphomas (THRBCL)
- Primary cutaneous DLBCL, leg type
- Intravascular large B cell lymphoma
- EBV+ DLBCL, NOS
- DLBCL associated with chronic inflammation
- HHV8+ DLBCL, NOS
- High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
- High grade B-cell lymphoma, NOS
- Follicular lymphoma grade 3b
- Participants must have staging imaging performed within 28 days prior to registration,
as follows. Positron emission tomography (PET)-computed tomography (CT) baseline scans
are strongly preferred; diagnostic quality magnetic resonance imaging (MRI),
contrast-enhanced CT, or contrast-enhanced MRI scans are also acceptable if PET-CT is
not feasible at baseline. Note: PET-CT will be required at end of treatment (EOT) and
progression for response assessment. All measurable lesions (longest diameter >= 1.5
cm) must be assessed within 28 days prior to registration. Tests to assess
non-measurable disease must be performed within 42 days prior to registration.
- Participants with known human immunodeficiency virus (HIV)-infection are eligible
providing they are on effective anti-retroviral therapy and have undetectable viral
load at their most recent viral load test (must be within 26 weeks prior to
registration). Participants with known HIV must have a CD4 count checked within 28
days prior to registration, but may proceed with therapy regardless of CD4 count.
- All participants must be screened for chronic hepatitis B virus (HBV) within 28 days
prior to registration. Participants with known HBV infection (positive serology) must
also have a HBV viral load performed within 28 days prior to registration, and
participants must have an undetectable HBV viral load on suppressive therapy within 28
days prior to registration. Participants found to be HBV carriers during screening are
eligible and must receive standard of care prophylaxis. Participants with active
hepatitis B (HBV viral load > 500 IU/mL) within 28 days prior to registration are not
eligible
- Participants with a known history of hepatitis C virus (HCV) infection must have an
undetectable HCV viral load within in 28 days prior to registration
- Participants must have a Zubrod performance status of 0-2
- Participants must have adequate renal function, as demonstrated by a creatinine
clearance, calculated by the Cockcroft and Gault formula, of >= 30 ml/min that was
obtained within 28 days prior to registration
- Aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (IULN),
alanine aminotransferase (ALT) =< 2.5 x IULN (within 28 days prior to registration)
- Total bilirubin =< 2 x institutional upper limit of normal (IULN), unless due to
Gilbert's disease, hemolysis, or lymphomatous involvement of liver (within 28 days
prior to registration). Note: If total bilirubin is elevated, and direct bilirubin is
subsequently performed (within 28 days prior to registration) and resulted to be =< 2
x IULN, the participant will be considered eligible
- Absolute neutrophil count (ANC) >= 1000/mcL (within 28 days prior to registration)
- Platelets >= 75,000/mcL (within 28 days prior to registration)
- Hemoglobin (Hgb) >= 8 g/ dL (within 28 days prior to registration)
- If there is a documented lymphomatous involvement of the bone marrow, bone marrow
function within 28 days prior to registration, as evidenced by:
- ANC >= 500/mcL
- Platelets >= 50,000/mcL
- Hemoglobin (Hgb) >= 8 g/ dL
- Participants must have a left ventricular ejection (LVEF) fraction >= 45% as measured
by echocardiogram or radionuclide (multigated acquisition scan [MUGA])
ventriculography within 56 days prior to registration
- For the duration of the study treatment period and for at least 4 months following the
last dose of study drug, male participants must agree to use effective contraceptive
methods during sexual contact with a female of childbearing potential (FCBP) and must
agree to refrain from semen or sperm donation during the same timeframe. Effective
contraceptive methods include a history of vasectomy, use of hormonal contraception or
an intrauterine device (IUD) by the female partner, or use of condoms
- A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or
bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least
24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months)
Exclusion Criteria:
- Participants must not have known lymphomatous involvement of the central nervous
system (CNS)
- Participants must not have active inflammatory bowel disease (such as, Crohn's
disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper
bowel removal, or any other gastrointestinal disorder or defect that would interfere
with the absorption, distribution, metabolism, or excretion of the study drug and/or
predispose the subject to an increased risk of gastrointestinal toxicity
- Participants must not have received any prior cytotoxic chemotherapy or rituximab for
treatment of the newly diagnosed DLBCL except for the pre-phase treatment (within
specified dose range) that may have either started before or may start after
registration to S1918. Inhaled, nasal, and topical steroid use is allowed. Prior
cytotoxic chemotherapy and/or antibody therapy for an indolent lymphoma prior to
transformation is allowed. Up to 4 doses of intrathecal (IT) chemotherapy administered
for central nervous system (CNS) prophylaxis is allowed in addition to protocol
therapy. High-dose intravenous methotrexate is not allowed.
- Participants must not have received more than a cumulative of dose 250 mg/m^2 of prior
doxorubicin (or equivalent dose of another anthracycline, such as epirubicin) therapy
(at any time prior to registration).
- Participants must not currently be receiving any other investigational agents
- Participant must not have a history of allergic reactions attributed to azacitidine,
mannitol, or other hypomethylating agents
- Participants must not have active infection (systemic fungal, bacterial, or viral
infection) that is not controlled (defined as ongoing signs/symptoms related the
infection without improvement despite appropriate antibiotics, antiviral therapy,
and/or other treatment)
- Participants must not have active cardiac disease within 26 weeks prior to
registration, including: symptomatic congestive heart failure (New York Heart
Association [NYHA] class 4), unstable angina pectoris, hemodynamically unstable
cardiac arrhythmia, or myocardial infarction
- Participants must not have >= grade 2 neuropathy, by Common Terminology Criteria for
Adverse Events (CTCAE) version (v.) 5.0, within 28 days prior to registration
- Participants must not have any other known uncontrolled intercurrent illness
including, but not limited to ongoing psychiatric illness/social situations that would
limit compliance with study requirements
Intervention(s):
drug: Cyclophosphamide
drug: Doxorubicin Hydrochloride
drug: Oral Azacitidine
drug: Prednisone
other: Questionnaire Administration
biological: Rituximab
drug: Vincristine Sulfate
Recruiting
I'm InterestedContact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
Daniel Heck
650-498-7061