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

Who is this study for? Patients with Lymphoma
What treatments are being studied? Cyclophosphamide+Doxorubicin+Vincristine+Prednisone+Etoposide
Status: Suspended
Location: See all (86) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

Locations
United States
Arkansas
University of Arkansas for Medical Sciences
Little Rock
California
City of Hope Comprehensive Cancer Center
Duarte
UC San Diego Moores Cancer Center
La Jolla
Cedars Sinai Medical Center
Los Angeles
Washington, D.c.
MedStar Georgetown University Hospital
Washington D.c.
Florida
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami
Georgia
Emory Saint Joseph's Hospital
Atlanta
Emory University Hospital Midtown
Atlanta
Emory University Hospital/Winship Cancer Institute
Atlanta
Grady Health System
Atlanta
Augusta University Medical Center
Augusta
Iowa
University of Iowa/Holden Comprehensive Cancer Center
Iowa City
Illinois
Northwestern University
Chicago
University of Chicago Comprehensive Cancer Center
Chicago
University of Illinois
Chicago
Northwestern Medicine Cancer Center Kishwaukee
Dekalb
Northwestern Medicine Cancer Center Delnor
Geneva
Northwestern Medicine Lake Forest Hospital
Lake Forest
AMG Libertyville - Oncology
Libertyville
Memorial Hospital East
Shiloh
Carle Cancer Center
Urbana
Northwestern Medicine Cancer Center Warrenville
Warrenville
Kansas
University of Kansas Cancer Center-Overland Park
Overland Park
University of Kansas Hospital-Westwood Cancer Center
Westwood
Louisiana
Our Lady of the Lake Physician Group
Baton Rouge
Massachusetts
Dana-Farber Cancer Institute
Boston
Michigan
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton
Minnesota
Mayo Clinic in Rochester
Rochester
Missouri
Saint Luke's Hospital
Chesterfield
Siteman Cancer Center at West County Hospital
Creve Coeur
Siteman Cancer Center at Christian Hospital
St Louis
Siteman Cancer Center-South County
St Louis
Washington University School of Medicine
St Louis
North Carolina
UNC Lineberger Comprehensive Cancer Center
Chapel Hill
Wake Forest University Health Sciences
Winston-salem
Nebraska
Nebraska Medicine-Bellevue
Bellevue
Nebraska Medicine-Village Pointe
Omaha
University of Nebraska Medical Center
Omaha
New Hampshire
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon
New Jersey
Memorial Sloan Kettering Basking Ridge
Basking Ridge
Memorial Sloan Kettering Monmouth
Middletown
Memorial Sloan Kettering Bergen
Montvale
New York
Roswell Park Cancer Institute
Buffalo
Memorial Sloan Kettering Commack
Commack
Memorial Sloan Kettering Westchester
Harrison
Memorial Sloan Kettering Cancer Center
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York
NYP/Weill Cornell Medical Center
New York
University of Rochester
Rochester
Memorial Sloan Kettering Nassau
Uniondale
Wilmot Cancer Institute at Webster
Webster
Ohio
Miami Valley Hospital South
Centerville
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati
Grant Medical Center
Columbus
Ohio State University Comprehensive Cancer Center
Columbus
Riverside Methodist Hospital
Columbus
Dayton Physician LLC - Englewood
Dayton
Miami Valley Hospital
Dayton
Miami Valley Hospital North
Dayton
Premier Blood and Cancer Center
Dayton
Delaware Health Center-Grady Cancer Center
Delaware
Atrium Medical Center-Middletown Regional Hospital
Franklin
Miami Valley Cancer Care and Infusion
Greenville
Greater Dayton Cancer Center
Kettering
Upper Valley Medical Center
Troy
University of Cincinnati Cancer Center-West Chester
West Chester
Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City
Pennsylvania
University of Pennsylvania/Abramson Cancer Center
Philadelphia
Rhode Island
Rhode Island Hospital
Providence
South Carolina
Medical University of South Carolina
Charleston
Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City
Virginia
University of Virginia Cancer Center
Charlottesville
Vermont
Dartmouth Cancer Center - North
Saint Johnsbury
Washington
Fred Hutchinson Cancer Center
Seattle
University of Washington Medical Center - Montlake
Seattle
Providence Saint Mary Regional Cancer Center
Walla Walla
Wisconsin
Marshfield Medical Center-EC Cancer Center
Eau Claire
Gundersen Lutheran Medical Center
La Crosse
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison
University of Wisconsin Carbone Cancer Center - University Hospital
Madison
Marshfield Medical Center-Marshfield
Marshfield
Marshfield Medical Center - Minocqua
Minocqua
Marshfield Medical Center-Rice Lake
Rice Lake
Marshfield Medical Center-River Region at Stevens Point
Stevens Point
Marshfield Medical Center - Weston
Weston
Time Frame
Start Date: 2021-10-08
Completion Date: 2026-06-30
Participants
Target number of participants: 170
Treatments
Experimental: Arm A (duvelisib, CHO[E]P)
Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on day 1 or days 1-3 or PO QD on days 2-3 for patients =\< 60 years old, and prednisone PO QD on days 1-5. Patients also receive duvelisib PO BID on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Experimental: Arm B (CC-486, CHO[E]P)
Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on day 1 or days 1-3 or PO 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.
Active_comparator: Arm C (CHO[E]P)
Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on day 1 or days 1-3 or PO 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.
Sponsors
Leads: Alliance for Clinical Trials in Oncology
Collaborators: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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