Non Hodgkin Lymphoma Clinical Trial
Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma
Summary
This phase II trial studies the effect of duvelisib or CC-486 and usual chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone in treating patients with peripheral T-cell lymphoma. Duvelisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as CC-486, cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, 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 may help find out if this approach is better or worse than the usual approach for treating peripheral T-cell lymphoma.
Full Description
PRIMARY OBJECTIVE:
I. To compare the complete remission (CR) rates by positron emission tomography (PET)/computed tomography (CT) following completion of treatment with duvelisib-cyclophosphamide (C) doxorubicin (H) vincristine (O) (etoposide [E]) prednisone (P) versus (vs) CHO(E)P and with oral azacitidine (CC-486)-CHO(E)P vs CHO(E)P in previously untreated peripheral T-cell lymphomas that have < 10% expression of CD30.
SECONDARY OBJECTIVES:
I. To determine the toxicity and tolerability of the treatment regimens. II. To determine the overall response rate (ORR), duration of response, progression free survival (PFS), event free survival (EFS), and overall survival (OS) of each treatment regimen.
III. To determine whether designation of follicular helper T-cell phenotype is correlated with response to therapy, PFS, EFS, and OS.
IV. To assess the toxicity profile of the experimental regimens in untreated CD30 negative peripheral T-cell lymphomas using Common Terminology Criteria for Adverse Events (CTCAE) and patient reported outcomes (PRO)-CTCAE.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM A: Patients receive cyclophosphamide intravenously (IV) on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO) once daily (QD) on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5. Patients also receive duvelisib PO twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO) once daily (QD) on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5. Patients also receive CC-486 PO QD on days -6 to 0 of cycle -1 and days 8-21 of cycles 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO) once daily (QD) on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 6 weeks after cycle 6 day 1, then every 12 weeks for 2 years, then every 24 weeks until 5 years from end of treatment or until documented progression of lymphoma. After documented progression of lymphoma, patients are followed up every 6 months until 5 years from end of treatment.
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10% CD30 expression by immunohistochemistry in the following subtypes (by local review): nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL), follicular T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma
Patients with expression of CD30 in >= 10% of the tumor (based on local immunohistochemistry review) regardless of histology will not be permitted
Patients with a diagnosis of other PTCL subtype histologies other than those specified in the inclusion criteria are excluded including large cell transformation of mycosis fungoides
Patients will be stratified by presence or absence of TFH phenotype (i.e. diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review of pathology. Determination of TFH phenotype can be defined by expression of two or more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by immunohistochemistry
Measurable disease as defined by the Lugano criteria
No prior systemic therapy for lymphoma (excluding corticosteroids)
Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to registration is required
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Platelet count >= 75,000/mm^3 (>= 50,000/mm^3 if secondary to bone marrow involvement from lymphoma per investigator assessment; the first 12 patients on each arm of the study must have platelets >= 75,000/mm^3 regardless of bone marrow involvement)
Absolute neutrophil count (ANC) >= 1,000/mm^3
Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3.0 x upper limit of normal (ULN)
* Except in subjects with documented liver involvement by lymphoma
Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
Total bilirubin =< 2.0 x ULN
* Except in cases of Gilbert's Syndrome or documented liver or pancreatic involvement by lymphoma
Archival tissue must be available for submission
Patients known to have HTLV 1/2 are excluded
Patients with known central nervous system involvement are excluded
No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Those who are seropositive (e.g. hepatitis B core antibody [Ab] positive) are permitted if they are negative by polymerase chain reaction (PCR). Those who are seropositive for hepatitis B and are negative for hepatitis B virus (HBV) deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B directed antiviral therapy. Those who have hepatitis C Ab positivity who have completed curative therapy for hepatitis C with negative hepatitis C PCR are eligible
Patients with history of HIV are eligible if they have an undetectable viral load for at least 6 months
No active uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment). Patients with Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted
No concurrent malignancy requiring active therapy within the last 3 years with the exception of basal cell carcinoma limited to the skin, squamous cell carcinoma limited to the skin, carcinoma in situ of the cervix, breast or localized prostate cancer. Adjuvant hormonal therapy for cancer previously treated for curative intent is permitted
Patients must have documented left ventricular ejection fraction of >= 45%
No significant active cardiac disease within the previous 6 months including:
New York Heart Association (NYHA) class III or IV congestive heart failure
Unstable angina or angina requiring surgical or medical intervention; and/or
Myocardial infarction
No contraindication to any drug in the chemotherapy regimen, including neuropathy >= grade 2
Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
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There are 65 Locations for this study
Duarte California, 91010, United States More Info
Principal Investigator
Los Angeles California, 90048, United States More Info
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Washington District of Columbia, 20007, United States More Info
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Miami Florida, 33136, United States More Info
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Atlanta Georgia, 30303, United States More Info
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Atlanta Georgia, 30308, United States More Info
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Atlanta Georgia, 30322, United States More Info
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Atlanta Georgia, 30342, United States More Info
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Chicago Illinois, 60611, United States More Info
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Chicago Illinois, 60612, United States
Chicago Illinois, 60637, United States
DeKalb Illinois, 60115, United States More Info
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Geneva Illinois, 60134, United States More Info
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Lake Forest Illinois, 60045, United States More Info
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Shiloh Illinois, 62269, United States More Info
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Urbana Illinois, 61801, United States More Info
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Warrenville Illinois, 60555, United States More Info
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Iowa City Iowa, 52242, United States More Info
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Overland Park Kansas, 66210, United States More Info
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Westwood Kansas, 66205, United States More Info
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Boston Massachusetts, 02215, United States More Info
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Brighton Michigan, 48114, United States More Info
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Rochester Minnesota, 55905, United States More Info
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Chesterfield Missouri, 63017, United States More Info
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Creve Coeur Missouri, 63141, United States More Info
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Saint Louis Missouri, 63110, United States More Info
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Saint Louis Missouri, 63129, United States More Info
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Bellevue Nebraska, 68123, United States More Info
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Omaha Nebraska, 68118, United States More Info
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Omaha Nebraska, 68198, United States More Info
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Lebanon New Hampshire, 03756, United States
Basking Ridge New Jersey, 07920, United States More Info
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Middletown New Jersey, 07748, United States More Info
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Montvale New Jersey, 07645, United States More Info
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Buffalo New York, 14263, United States More Info
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Commack New York, 11725, United States More Info
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Harrison New York, 10604, United States More Info
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New York New York, 10032, United States More Info
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New York New York, 10065, United States More Info
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New York New York, 10065, United States More Info
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Rochester New York, 14642, United States More Info
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Uniondale New York, 11553, United States More Info
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Webster New York, 14580, United States More Info
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Chapel Hill North Carolina, 27599, United States More Info
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Winston-Salem North Carolina, 27157, United States More Info
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Cincinnati Ohio, 45219, United States More Info
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Columbus Ohio, 43210, United States More Info
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Dayton Ohio, 45415, United States
Kettering Ohio, 45409, United States More Info
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West Chester Ohio, 45069, United States More Info
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Oklahoma City Oklahoma, 73104, United States More Info
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Philadelphia Pennsylvania, 19104, United States More Info
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Providence Rhode Island, 02903, United States More Info
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Charleston South Carolina, 29425, United States More Info
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Salt Lake City Utah, 84112, United States More Info
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Saint Johnsbury Vermont, 05819, United States More Info
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Seattle Washington, 98109, United States More Info
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Seattle Washington, 98109, United States More Info
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Seattle Washington, 98195, United States More Info
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Walla Walla Washington, 99362, United States More Info
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Eau Claire Wisconsin, 54701, United States More Info
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La Crosse Wisconsin, 54601, United States More Info
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Madison Wisconsin, 53792, United States More Info
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Marshfield Wisconsin, 54449, United States More Info
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Minocqua Wisconsin, 54548, United States More Info
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Stevens Point Wisconsin, 54482, United States More Info
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Weston Wisconsin, 54476, United States More Info
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