Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma

September 1, 2026 updated by: Alliance for Clinical Trials in Oncology

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

170

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Neha Mehta-Shah, MD, MSCI
  • Phone Number: 314-747-7510
  • Email: mehta-n@wustl.edu

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • University of Arkansas for Medical Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 501-686-8274
        • Principal Investigator:
          • Mamatha Gaddam
    • California
      • Duarte, California, United States, 91010
        • Active, not recruiting
        • City of Hope Comprehensive Cancer Center
      • La Jolla, California, United States, 92093
        • Active, not recruiting
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Principal Investigator:
          • Akil A. Merchant
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Active, not recruiting
        • MedStar Georgetown University Hospital
    • Florida
      • Deerfield Beach, Florida, United States, 33442
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Jonathan H. Schatz
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Jonathan H. Schatz
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital/Winship Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 404-778-1868
        • Principal Investigator:
          • Pamela B. Allen
      • Atlanta, Georgia, United States, 30303
        • Recruiting
        • Grady Health System
        • Contact:
          • Site Public Contact
          • Phone Number: 404-778-1868
        • Principal Investigator:
          • Pamela B. Allen
      • Atlanta, Georgia, United States, 30308
        • Recruiting
        • Emory University Hospital Midtown
        • Contact:
          • Site Public Contact
          • Phone Number: 888-946-7447
        • Principal Investigator:
          • Pamela B. Allen
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Emory Saint Joseph's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 404-851-7115
        • Principal Investigator:
          • Pamela B. Allen
      • Augusta, Georgia, United States, 30912
        • Recruiting
        • Augusta University Medical Center
        • Principal Investigator:
          • Locke J. Bryan
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Principal Investigator:
          • Jonathan Moreira
        • Contact:
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois
        • Contact:
          • Site Public Contact
          • Phone Number: 312-355-3046
        • Principal Investigator:
          • Paul G. Rubinstein
      • Chicago, Illinois, United States, 60637
        • Completed
        • University of Chicago Comprehensive Cancer Center
      • DeKalb, Illinois, United States, 60115
        • Recruiting
        • Northwestern Medicine Cancer Center Kishwaukee
        • Principal Investigator:
          • Jonathan Moreira
        • Contact:
      • Geneva, Illinois, United States, 60134
        • Recruiting
        • Northwestern Medicine Cancer Center Delnor
        • Principal Investigator:
          • Jonathan Moreira
        • Contact:
      • Lake Forest, Illinois, United States, 60045
        • Recruiting
        • Northwestern Medicine Lake Forest Hospital
        • Principal Investigator:
          • Jonathan Moreira
        • Contact:
      • Libertyville, Illinois, United States, 60048
        • Recruiting
        • AMG Libertyville - Oncology
        • Contact:
        • Principal Investigator:
          • Peter J. Polewski
      • Shiloh, Illinois, United States, 62269
        • Recruiting
        • Memorial Hospital East
        • Contact:
        • Principal Investigator:
          • Neha Mehta-Shah
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Tanmay Sahai
      • Warrenville, Illinois, United States, 60555
        • Recruiting
        • Northwestern Medicine Cancer Center Warrenville
        • Principal Investigator:
          • Jonathan Moreira
        • Contact:
    • Iowa
      • Ankeny, Iowa, United States, 50023
        • Recruiting
        • UI Health Care Mission Cancer and Blood - Ankeny Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • Iowa Methodist Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-6727
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • UI Health Care Mission Cancer and Blood - Des Moines Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Des Moines, Iowa, United States, 50314
        • Recruiting
        • UI Health Care Mission Cancer and Blood - Laurel Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa/Holden Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-237-1225
        • Principal Investigator:
          • Eric Mou
      • Waukee, Iowa, United States, 50263
        • Recruiting
        • UI Health Care Mission Cancer and Blood - Waukee Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
    • Kansas
      • Overland Park, Kansas, United States, 66210
        • Recruiting
        • University of Kansas Cancer Center-Overland Park
        • Principal Investigator:
          • Marc S. Hoffmann
        • Contact:
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Hospital-Westwood Cancer Center
        • Principal Investigator:
          • Marc S. Hoffmann
        • Contact:
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky/Markey Cancer Center
        • Principal Investigator:
          • Chaitanya Iragavarapu
        • Contact:
          • Site Public Contact
          • Phone Number: 859-257-3379
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70808
        • Recruiting
        • Our Lady of the Lake Physician Group
        • Contact:
        • Principal Investigator:
          • Nakhle S. Saba
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland/Greenebaum Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-888-8823
        • Principal Investigator:
          • Kathryn Kline
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 877-442-3324
        • Principal Investigator:
          • Eric D. Jacobsen
    • Michigan
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • Recruiting
        • Essentia Health Cancer Center
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Nabila N. Bennani
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • Recruiting
        • Saint Luke's Hospital
        • Principal Investigator:
          • Mark J. Fesler
        • Contact:
          • Site Public Contact
          • Phone Number: 314-205-6936
      • Creve Coeur, Missouri, United States, 63141
        • Recruiting
        • Siteman Cancer Center at West County Hospital
        • Contact:
        • Principal Investigator:
          • Neha Mehta-Shah
      • Springfield, Missouri, United States, 65804
        • Suspended
        • Mercy Hospital Springfield
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Neha Mehta-Shah
      • St Louis, Missouri, United States, 63129
        • Recruiting
        • Siteman Cancer Center-South County
        • Contact:
        • Principal Investigator:
          • Neha Mehta-Shah
      • St Louis, Missouri, United States, 63136
        • Recruiting
        • Siteman Cancer Center at Christian Hospital
        • Contact:
        • Principal Investigator:
          • Neha Mehta-Shah
    • Nebraska
      • Bellevue, Nebraska, United States, 68123
        • Recruiting
        • Nebraska Medicine-Bellevue
        • Principal Investigator:
          • Matthew A. Lunning
        • Contact:
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Principal Investigator:
          • Matthew A. Lunning
        • Contact:
      • Omaha, Nebraska, United States, 68118
        • Recruiting
        • Nebraska Medicine-Village Pointe
        • Principal Investigator:
          • Matthew A. Lunning
        • Contact:
          • Site Public Contact
          • Phone Number: 402-559-5600
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Recruiting
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
        • Contact:
        • Principal Investigator:
          • Frederick Lansigan
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering Basking Ridge
        • Principal Investigator:
          • Alison J. Moskowitz
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
      • Camden, New Jersey, United States, 08103
        • Recruiting
        • Cooper Hospital University Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 856-325-6757
        • Principal Investigator:
          • Anil K. Rengan
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth
        • Principal Investigator:
          • Alison J. Moskowitz
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen
        • Principal Investigator:
          • Alison J. Moskowitz
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
    • New York
      • Buffalo, New York, United States, 14263
        • Active, not recruiting
        • Roswell Park Cancer Institute
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Commack
        • Principal Investigator:
          • Alison J. Moskowitz
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester
        • Principal Investigator:
          • Alison J. Moskowitz
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
      • New York, New York, United States, 10032
        • Recruiting
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • Principal Investigator:
          • Jennifer E. Amengual
        • Contact:
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Alison J. Moskowitz
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
      • New York, New York, United States, 10065
        • Recruiting
        • NYP/Weill Cornell Medical Center
        • Principal Investigator:
          • Jia Ruan
        • Contact:
          • Site Public Contact
          • Phone Number: 212-746-1848
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 585-275-5830
        • Principal Investigator:
          • Carla Casulo
      • Uniondale, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau
        • Principal Investigator:
          • Alison J. Moskowitz
        • Contact:
          • Site Public Contact
          • Phone Number: 212-639-7592
      • Webster, New York, United States, 14580
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • UNC Lineberger Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Anne W. Beaven
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
        • Principal Investigator:
          • Mary B. Seegars
    • Ohio
      • Centerville, Ohio, United States, 45459
        • Recruiting
        • Miami Valley Hospital South
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Cancer Center-UC Medical Center
        • Principal Investigator:
          • Tahir Latif
        • Contact:
      • Columbus, Ohio, United States, 43214
        • Recruiting
        • Riverside Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Basem M. William
      • Columbus, Ohio, United States, 43215
        • Recruiting
        • Grant Medical Center
        • Contact:
        • Principal Investigator:
          • Basem M. William
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Jonathan E. Brammer
      • Dayton, Ohio, United States, 45409
        • Recruiting
        • Miami Valley Hospital
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45415
        • Recruiting
        • Miami Valley Hospital North
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45409
        • Recruiting
        • Premier Blood and Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 937-276-8320
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45415
        • Suspended
        • Dayton Physician LLC - Englewood
      • Delaware, Ohio, United States, 43015
        • Recruiting
        • Delaware Health Center-Grady Cancer Center
        • Contact:
        • Principal Investigator:
          • Basem M. William
      • Franklin, Ohio, United States, 45005-1066
        • Recruiting
        • Atrium Medical Center-Middletown Regional Hospital
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Greenville, Ohio, United States, 45331
        • Recruiting
        • Miami Valley Cancer Care and Infusion
        • Principal Investigator:
          • Tarek M. Sabagh
        • Contact:
          • Site Public Contact
          • Phone Number: 937-569-7515
      • Kettering, Ohio, United States, 45409
        • Suspended
        • Greater Dayton Cancer Center
      • Troy, Ohio, United States, 45373
        • Recruiting
        • Upper Valley Medical Center
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • West Chester, Ohio, United States, 45069
        • Recruiting
        • University of Cincinnati Cancer Center-West Chester
        • Principal Investigator:
          • Tahir Latif
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Taha Al-Juhaishi
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania/Abramson Cancer Center
        • Principal Investigator:
          • Stefan K. Barta
        • Contact:
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Suspended
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
        • Principal Investigator:
          • Brian T. Hess
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute/University of Utah
        • Contact:
        • Principal Investigator:
          • Harsh Shah
    • Vermont
      • Saint Johnsbury, Vermont, United States, 05819
        • Recruiting
        • Dartmouth Cancer Center - North
        • Contact:
        • Principal Investigator:
          • Frederick Lansigan
    • Virginia
      • Charlottesville, Virginia, United States, 22908
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington Medical Center - Montlake
        • Principal Investigator:
          • Ajay K. Gopal
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-8824
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Center
        • Principal Investigator:
          • Ajay K. Gopal
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-8824
      • Walla Walla, Washington, United States, 99362
        • Recruiting
        • Providence Saint Mary Regional Cancer Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
      • La Crosse, Wisconsin, United States, 54601
        • Active, not recruiting
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center - University Hospital
        • Principal Investigator:
          • Saurabh Rajguru
        • Contact:
      • Madison, Wisconsin, United States, 53718
        • Recruiting
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
        • Principal Investigator:
          • Saurabh Rajguru
        • Contact:
      • Marshfield, Wisconsin, United States, 54449
      • Minocqua, Wisconsin, United States, 54548
      • Rice Lake, Wisconsin, United States, 54868
      • Stevens Point, Wisconsin, United States, 54482
      • Weston, Wisconsin, United States, 54476

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Cyclophosphamide
Given IV
Drug: Prednisone
Given PO
Drug: Vincristine
Given IV
Drug: Doxorubicin
Given IV
Drug: Duvelisib
Given PO
Drug: Etoposide
Given IV or PO
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.
Drug: Cyclophosphamide
Given IV
Drug: Prednisone
Given PO
Drug: Vincristine
Given IV
Drug: Doxorubicin
Given IV
Drug: Etoposide
Given IV or PO
Drug: Oral azacitidine
Given PO
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.
Drug: Cyclophosphamide
Given IV
Drug: Prednisone
Given PO
Drug: Vincristine
Given IV
Drug: Doxorubicin
Given IV
Drug: Etoposide
Given IV or PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission (CR) rate
Time Frame: Up to 6 months
Defined as the number of patients with complete remission (CR) divided by the total number of patients randomized. Will be measured by fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/computed tomography (CT) at the completion of treatment (at end of treatment) and will be compared between each experimental arm and control arm. Final analyses will use z-scores obtained from a stratified Cochran-Mantel-Haenszel test to compare the CR rates between each experimental arm and control arm. For each treatment arm, CR rates will be estimated with their 95% confidence intervals.
Up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: Up to 5 years
Adverse events will be collected and graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. For CTCAE data, the maximum grade for each type of adverse will be recorded for each patient, and described using frequency tables. All-cause adverse events will be summarized as well as treatment-related adverse events.
Up to 5 years
Overall response rate (ORR)
Time Frame: Up to 6 months
Overall response includes complete and partial remissions by FDG PET/CT at the completion of treatment (at end of treatment). ORR will be estimated for each treatment arm and calculated as the number of patients with response divided by the total number of patients randomized. For each treatment arm, ORRs will be estimated with their 95% confidence intervals. ORR at the interim assessment will be summarized in the same manner, and how response changes between the interim and final assessment will be described.
Up to 6 months
Duration of response
Time Frame: From first date of complete or partial remission until the earlier of disease progression, death from any cause, or non-protocol lymphoma-directed therapy to treat residual or progressive disease, assessed up to 5 years
The Kaplan-Meier method will be used to estimate duration of response for each treatment arm, with 2-year estimates and medians along with their 95% confidence intervals.
From first date of complete or partial remission until the earlier of disease progression, death from any cause, or non-protocol lymphoma-directed therapy to treat residual or progressive disease, assessed up to 5 years
Progression-free Survival (PFS)
Time Frame: From randomization date until the earlier of disease progression, death from any cause, or non-protocol lymphoma-directed therapy to treat residual or progressive disease, assessed up to 5 years
The Kaplan-Meier method will be used to estimate PFS for each treatment arm, with 2-year PFS estimates and PFS medians along with their 95% confidence intervals.
From randomization date until the earlier of disease progression, death from any cause, or non-protocol lymphoma-directed therapy to treat residual or progressive disease, assessed up to 5 years
Event-free Survival (EFS)
Time Frame: From randomization date until earlier of non-protocol lymphoma-directed therapy for any reason (excluding planned consolidative transplant), disease progression, or death from any cause, assessed up to 5 years
The Kaplan-Meier method will be used to estimate event-free survival (EFS) for each treatment arm, with 2-year EFS estimates and EFS medians along with their 95% confidence intervals.
From randomization date until earlier of non-protocol lymphoma-directed therapy for any reason (excluding planned consolidative transplant), disease progression, or death from any cause, assessed up to 5 years
Overall Survival (OS)
Time Frame: From randomization date until death from any cause, censoring patients alive at the date of last contact, assessed up to 5 years
The Kaplan-Meier method will be used to estimate overall survival (OS) for each treatment arm, with 2-year OS estimates and OS medians along with their 95% confidence intervals.
From randomization date until death from any cause, censoring patients alive at the date of last contact, assessed up to 5 years
Correlation of follicular helper T-cell phenotype with response, PFS, EFS and OS
Time Frame: Up to 5 years
CR rates and ORRs will be estimated with 95% confidence intervals for patients with and without the follicular helper T-cell phenotype, as well for patients with the peripheral T-cell lymphomas (PTCL) genotype.
Up to 5 years
Patient reported outcomes (PROs)
Time Frame: Up to 6 months
Patient reported outcomes (PROs) will be captured using the NCI PRO-CTCAE. Scores (0-4) and maximum score for each PRO-CTCAE item, with and without taking into account whether it is worse than the patient's own baseline score, will be recorded for each patient. PRO-CTCAE data will, at minimum, be analyzed similarly to CTCAE data.
Up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Neha Mehta-Shah, MD, MSCI, Washington University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2021

Primary Completion (Estimated)

May 19, 2027

Study Completion (Estimated)

May 19, 2027

Study Registration Dates

First Submitted

March 15, 2021

First Submitted That Met QC Criteria

March 15, 2021

First Posted (Actual)

March 17, 2021

Study Record Updates

Last Update Posted (Actual)

September 2, 2026

Last Update Submitted That Met QC Criteria

September 1, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A051902
  • U10CA180821 (U.S. NIH Grant/Contract)
  • NCI-2021-01380 (Registry Identifier: NCI Clinical Trial Reporting Program)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe