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

NCT ID: NCT04803201

Last Updated: 2025-09-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE2

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-08

Study Completion Date

2026-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Angioimmunoblastic T-cell Lymphoma Enteropathy-Associated T-Cell Lymphoma Follicular T-Cell Lymphoma Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma Nodal Peripheral T-Cell Lymphoma With TFH Phenotype Peripheral T-Cell Lymphoma, Not Otherwise Specified

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO

Etoposide

Intervention Type DRUG

Given IV or PO

Duvelisib

Intervention Type DRUG

Given PO

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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO

Etoposide

Intervention Type DRUG

Given IV or PO

Oral azacitidine

Intervention Type DRUG

Given PO

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.

Group Type ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type DRUG

Given IV

Doxorubicin

Intervention Type DRUG

Given IV

Vincristine

Intervention Type DRUG

Given IV

Prednisone

Intervention Type DRUG

Given PO

Etoposide

Intervention Type DRUG

Given IV or PO

Interventions

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Cyclophosphamide

Given IV

Intervention Type DRUG

Doxorubicin

Given IV

Intervention Type DRUG

Vincristine

Given IV

Intervention Type DRUG

Prednisone

Given PO

Intervention Type DRUG

Etoposide

Given IV or PO

Intervention Type DRUG

Duvelisib

Given PO

Intervention Type DRUG

Oral azacitidine

Given PO

Intervention Type DRUG

Eligibility Criteria

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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 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Neha Mehta-Shah, MD, MSCI

Role: STUDY_CHAIR

Washington University School of Medicine

Locations

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

Grady Health System

Atlanta, Georgia, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Site Status

Augusta University Medical Center

Augusta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, United States

Site Status

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, United States

Site Status

AMG Libertyville - Oncology

Libertyville, Illinois, United States

Site Status

Memorial Hospital East

Shiloh, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States

Site Status

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States

Site Status

Our Lady of the Lake Physician Group

Baton Rouge, Louisiana, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Saint Luke's Hospital

Chesterfield, Missouri, United States

Site Status

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Siteman Cancer Center-South County

St Louis, Missouri, United States

Site Status

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, United States

Site Status

Nebraska Medicine-Bellevue

Bellevue, Nebraska, United States

Site Status

Nebraska Medicine-Village Pointe

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, United States

Site Status

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status

Wilmot Cancer Institute at Webster

Webster, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Miami Valley Hospital South

Centerville, Ohio, United States

Site Status

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Grant Medical Center

Columbus, Ohio, United States

Site Status

Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Premier Blood and Cancer Center

Dayton, Ohio, United States

Site Status

Dayton Physician LLC - Englewood

Dayton, Ohio, United States

Site Status

Miami Valley Hospital North

Dayton, Ohio, United States

Site Status

Delaware Health Center-Grady Cancer Center

Delaware, Ohio, United States

Site Status

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, United States

Site Status

Miami Valley Cancer Care and Infusion

Greenville, Ohio, United States

Site Status

Greater Dayton Cancer Center

Kettering, Ohio, United States

Site Status

Upper Valley Medical Center

Troy, Ohio, United States

Site Status

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status

University of Washington Medical Center - Montlake

Seattle, Washington, United States

Site Status

Providence Saint Mary Regional Cancer Center

Walla Walla, Washington, United States

Site Status

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, United States

Site Status

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Site Status

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Site Status

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin, United States

Site Status

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin, United States

Site Status

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, United States

Site Status

Marshfield Medical Center - Weston

Weston, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2021-01380

Identifier Type: REGISTRY

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

A051902

Identifier Type: -

Identifier Source: org_study_id

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