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Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma
NCT04803201 · Alliance for Clinical Trials in Oncology
In plain English
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Official title
A Randomized Phase II Study of CHO(E)P vs CC-486-CHO(E)P vs Duvelisib-CHO(E)P in Previously Untreated CD30 Negative Peripheral T-Cell Lymphomas
About this study
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
Study design
Enrollment target: 170 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2021-10-08
Estimated completion: 2027-05-19
Last updated: 2026-09-02
Interventions
Drug: CyclophosphamideDrug: DoxorubicinDrug: VincristineDrug: PrednisoneDrug: EtoposideDrug: DuvelisibDrug: Oral azacitidine
Primary outcomes
- • Complete remission (CR) rate (Up to 6 months)
Sponsor
Alliance for Clinical Trials in Oncology · other
With: National Cancer Institute (NCI)
Contacts & investigators
ContactNeha Mehta-Shah, MD, MSCI · contact · mehta-n@wustl.edu · 314-747-7510
InvestigatorNeha Mehta-Shah, MD, MSCI · study_chair, Washington University School of Medicine
All locations (96)
University of Arkansas for Medical SciencesRecruiting
Little Rock, Arkansas, United States
City of Hope Comprehensive Cancer CenterActive Not Recruiting
Duarte, California, United States
UC San Diego Moores Cancer CenterActive Not Recruiting
La Jolla, California, United States
Cedars-Sinai Medical CenterRecruiting
Los Angeles, California, United States
MedStar Georgetown University HospitalActive Not Recruiting
Washington D.C., District of Columbia, United States
UM Sylvester Comprehensive Cancer Center at Deerfield BeachRecruiting
Deerfield Beach, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
Miami, Florida, United States
Grady Health SystemRecruiting
Atlanta, Georgia, United States
Emory University Hospital MidtownRecruiting
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer InstituteRecruiting
Atlanta, Georgia, United States
Emory Saint Joseph's HospitalRecruiting
Atlanta, Georgia, United States
Augusta University Medical CenterRecruiting
Augusta, Georgia, United States
Northwestern UniversityRecruiting
Chicago, Illinois, United States
University of IllinoisRecruiting
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer CenterCompleted
Chicago, Illinois, United States
Northwestern Medicine Cancer Center KishwaukeeRecruiting
DeKalb, Illinois, United States
Northwestern Medicine Cancer Center DelnorRecruiting
Geneva, Illinois, United States
Northwestern Medicine Lake Forest HospitalRecruiting
Lake Forest, Illinois, United States
AMG Libertyville - OncologyRecruiting
Libertyville, Illinois, United States
Memorial Hospital EastRecruiting
Shiloh, Illinois, United States
Carle Cancer CenterRecruiting
Urbana, Illinois, United States
Northwestern Medicine Cancer Center WarrenvilleRecruiting
Warrenville, Illinois, United States
UI Health Care Mission Cancer and Blood - Ankeny ClinicRecruiting
Ankeny, Iowa, United States
Iowa Methodist Medical CenterRecruiting
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines ClinicRecruiting
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Laurel ClinicRecruiting
Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer CenterRecruiting
Iowa City, Iowa, United States
UI Health Care Mission Cancer and Blood - Waukee ClinicRecruiting
Waukee, Iowa, United States
University of Kansas Cancer Center-Overland ParkRecruiting
Overland Park, Kansas, United States
University of Kansas Hospital-Westwood Cancer CenterRecruiting
Westwood, Kansas, United States
University of Kentucky/Markey Cancer CenterRecruiting
Lexington, Kentucky, United States
Our Lady of the Lake Physician GroupRecruiting
Baton Rouge, Louisiana, United States
University of Maryland/Greenebaum Cancer CenterRecruiting
Baltimore, Maryland, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Trinity Health IHA Medical Group Hematology Oncology - BrightonRecruiting
Brighton, Michigan, United States
Essentia Health Cancer CenterRecruiting
Duluth, Minnesota, United States
Mayo Clinic in RochesterRecruiting
Rochester, Minnesota, United States
Saint Luke's HospitalRecruiting
Chesterfield, Missouri, United States
Siteman Cancer Center at West County HospitalRecruiting
Creve Coeur, Missouri, United States
Mercy Hospital SpringfieldSuspended
Springfield, Missouri, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Siteman Cancer Center-South CountyRecruiting
St Louis, Missouri, United States
Siteman Cancer Center at Christian HospitalRecruiting
St Louis, Missouri, United States
Nebraska Medicine-BellevueRecruiting
Bellevue, Nebraska, United States
Nebraska Medicine-Village PointeRecruiting
Omaha, Nebraska, United States
University of Nebraska Medical CenterRecruiting
Omaha, Nebraska, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
Lebanon, New Hampshire, United States
Memorial Sloan Kettering Basking RidgeRecruiting
Basking Ridge, New Jersey, United States
Cooper Hospital University Medical CenterRecruiting
Camden, New Jersey, United States
Memorial Sloan Kettering MonmouthRecruiting
Middletown, New Jersey, United States
Memorial Sloan Kettering BergenRecruiting
Montvale, New Jersey, United States
Roswell Park Cancer InstituteActive Not Recruiting
Buffalo, New York, United States
Memorial Sloan Kettering CommackRecruiting
Commack, New York, United States
Memorial Sloan Kettering WestchesterRecruiting
Harrison, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
NYP/Weill Cornell Medical CenterRecruiting
New York, New York, United States
University of RochesterRecruiting
Rochester, New York, United States
Memorial Sloan Kettering NassauRecruiting
Uniondale, New York, United States
Wilmot Cancer Institute at WebsterRecruiting
Webster, New York, United States
UNC Lineberger Comprehensive Cancer CenterRecruiting
Chapel Hill, North Carolina, United States
Wake Forest University Health SciencesRecruiting
Winston-Salem, North Carolina, United States
Miami Valley Hospital SouthRecruiting
Centerville, Ohio, United States
University of Cincinnati Cancer Center-UC Medical CenterRecruiting
Cincinnati, Ohio, United States
Ohio State University Comprehensive Cancer CenterRecruiting
Columbus, Ohio, United States
Riverside Methodist HospitalRecruiting
Columbus, Ohio, United States
Grant Medical CenterRecruiting
Columbus, Ohio, United States
Miami Valley HospitalRecruiting
Dayton, Ohio, United States
Premier Blood and Cancer CenterRecruiting
Dayton, Ohio, United States
Dayton Physician LLC - EnglewoodSuspended
Dayton, Ohio, United States
Miami Valley Hospital NorthRecruiting
Dayton, Ohio, United States
Delaware Health Center-Grady Cancer CenterRecruiting
Delaware, Ohio, United States
Atrium Medical Center-Middletown Regional HospitalRecruiting
Franklin, Ohio, United States
Miami Valley Cancer Care and InfusionRecruiting
Greenville, Ohio, United States
Greater Dayton Cancer CenterSuspended
Kettering, Ohio, United States
Upper Valley Medical CenterRecruiting
Troy, Ohio, United States
University of Cincinnati Cancer Center-West ChesterRecruiting
West Chester, Ohio, United States
University of Oklahoma Health Sciences CenterRecruiting
Oklahoma City, Oklahoma, United States
University of Pennsylvania/Abramson Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
Rhode Island HospitalSuspended
Providence, Rhode Island, United States
Medical University of South CarolinaRecruiting
Charleston, South Carolina, United States
Huntsman Cancer Institute/University of UtahRecruiting
Salt Lake City, Utah, United States
Dartmouth Cancer Center - NorthRecruiting
Saint Johnsbury, Vermont, United States
University of Virginia Cancer CenterRecruiting
Charlottesville, Virginia, United States
Fred Hutchinson Cancer CenterRecruiting
Seattle, Washington, United States
University of Washington Medical Center - MontlakeRecruiting
Seattle, Washington, United States
Providence Saint Mary Regional Cancer CenterRecruiting
Walla Walla, Washington, United States
Marshfield Medical Center-EC Cancer CenterRecruiting
Eau Claire, Wisconsin, United States
Gundersen Lutheran Medical CenterActive Not Recruiting
La Crosse, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical CenterRecruiting
Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University HospitalRecruiting
Madison, Wisconsin, United States
Marshfield Medical Center-MarshfieldRecruiting
Marshfield, Wisconsin, United States
Marshfield Medical Center - MinocquaRecruiting
Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice LakeRecruiting
Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens PointRecruiting
Stevens Point, Wisconsin, United States
Marshfield Medical Center - WestonRecruiting
Weston, Wisconsin, United States