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.

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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.

View Eligibility Criteria

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 is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

170

Study ID:

NCT04803201

Recruitment Status:

Recruiting

Sponsor:

Alliance for Clinical Trials in Oncology

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There are 65 Locations for this study

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City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States More Info
Site Public Contact
Contact
800-826-4673
[email protected]
Jasmine M. Zain
Principal Investigator
Cedars Sinai Medical Center
Los Angeles California, 90048, United States More Info
Site Public Contact
Contact
310-423-8965
Akil A. Merchant
Principal Investigator
MedStar Georgetown University Hospital
Washington District of Columbia, 20007, United States More Info
Site Public Contact
Contact
202-444-2223
Joseph L. Roswarski
Principal Investigator
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami Florida, 33136, United States More Info
Site Public Contact
Contact
305-243-2647
Jonathan H. Schatz
Principal Investigator
Grady Health System
Atlanta Georgia, 30303, United States More Info
Site Public Contact
Contact
404-489-9164
Pamela B. Allen
Principal Investigator
Emory University Hospital Midtown
Atlanta Georgia, 30308, United States More Info
Site Public Contact
Contact
888-946-7447
Pamela B. Allen
Principal Investigator
Emory University Hospital/Winship Cancer Institute
Atlanta Georgia, 30322, United States More Info
Site Public Contact
Contact
404-778-1868
Pamela B. Allen
Principal Investigator
Emory Saint Joseph's Hospital
Atlanta Georgia, 30342, United States More Info
Site Public Contact
Contact
404-851-7115
Pamela B. Allen
Principal Investigator
Northwestern University
Chicago Illinois, 60611, United States More Info
Site Public Contact
Contact
312-695-1301
[email protected]
Jonathan Moreira
Principal Investigator
University of Illinois
Chicago Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago Illinois, 60637, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb Illinois, 60115, United States More Info
Site Public Contact
Contact
630-352-5360
[email protected]
Jonathan Moreira
Principal Investigator
Northwestern Medicine Cancer Center Delnor
Geneva Illinois, 60134, United States More Info
Site Public Contact
Contact
630-352-5360
[email protected]
Jonathan Moreira
Principal Investigator
Northwestern Medicine Lake Forest Hospital
Lake Forest Illinois, 60045, United States More Info
Site Public Contact
Contact
[email protected]
Jonathan Moreira
Principal Investigator
Memorial Hospital East
Shiloh Illinois, 62269, United States More Info
Site Public Contact
Contact
314-747-9912
[email protected]
Neha Mehta-Shah
Principal Investigator
Carle Cancer Center
Urbana Illinois, 61801, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Tanmay Sahai
Principal Investigator
Northwestern Medicine Cancer Center Warrenville
Warrenville Illinois, 60555, United States More Info
Site Public Contact
Contact
630-352-5360
[email protected]
Jonathan Moreira
Principal Investigator
University of Iowa/Holden Comprehensive Cancer Center
Iowa City Iowa, 52242, United States More Info
Site Public Contact
Contact
800-237-1225
Umar Farooq
Principal Investigator
University of Kansas Cancer Center-Overland Park
Overland Park Kansas, 66210, United States More Info
Site Public Contact
Contact
913-588-3671
[email protected]
Marc S. Hoffmann
Principal Investigator
University of Kansas Hospital-Westwood Cancer Center
Westwood Kansas, 66205, United States More Info
Site Public Contact
Contact
913-588-3671
[email protected]
Marc S. Hoffmann
Principal Investigator
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States More Info
Site Public Contact
Contact
877-442-3324
Eric D. Jacobsen
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton Michigan, 48114, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Elie G. Dib
Principal Investigator
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States More Info
Site Public Contact
Contact
855-776-0015
Nabila N. Bennani
Principal Investigator
Saint Luke's Hospital
Chesterfield Missouri, 63017, United States More Info
Site Public Contact
Contact
314-205-6936
Joseph Sokhn
Principal Investigator
Siteman Cancer Center at West County Hospital
Creve Coeur Missouri, 63141, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Neha Mehta-Shah
Principal Investigator
Washington University School of Medicine
Saint Louis Missouri, 63110, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Neha Mehta-Shah
Principal Investigator
Siteman Cancer Center-South County
Saint Louis Missouri, 63129, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Neha Mehta-Shah
Principal Investigator
Nebraska Medicine-Bellevue
Bellevue Nebraska, 68123, United States More Info
Site Public Contact
Contact
402-559-6941
[email protected]
Matthew A. Lunning
Principal Investigator
Nebraska Medicine-Village Pointe
Omaha Nebraska, 68118, United States More Info
Site Public Contact
Contact
402-559-5600
Matthew A. Lunning
Principal Investigator
University of Nebraska Medical Center
Omaha Nebraska, 68198, United States More Info
Site Public Contact
Contact
402-559-6941
[email protected]
Matthew A. Lunning
Principal Investigator
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon New Hampshire, 03756, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge New Jersey, 07920, United States More Info
Site Public Contact
Contact
212-639-7592
Alison J. Moskowitz
Principal Investigator
Memorial Sloan Kettering Monmouth
Middletown New Jersey, 07748, United States More Info
Site Public Contact
Contact
212-639-7592
Alison J. Moskowitz
Principal Investigator
Memorial Sloan Kettering Bergen
Montvale New Jersey, 07645, United States More Info
Site Public Contact
Contact
212-639-7592
Alison J. Moskowitz
Principal Investigator
Roswell Park Cancer Institute
Buffalo New York, 14263, United States More Info
Site Public Contact
Contact
800-767-9355
[email protected]
Francisco J. Hernandez-ILizaliturri
Principal Investigator
Memorial Sloan Kettering Commack
Commack New York, 11725, United States More Info
Site Public Contact
Contact
212-639-7592
Alison J. Moskowitz
Principal Investigator
Memorial Sloan Kettering Westchester
Harrison New York, 10604, United States More Info
Site Public Contact
Contact
212-639-7592
Alison J. Moskowitz
Principal Investigator
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York New York, 10032, United States More Info
Site Public Contact
Contact
212-342-5162
[email protected]
Jennifer E. Amengual
Principal Investigator
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States More Info
Site Public Contact
Contact
212-639-7592
Alison J. Moskowitz
Principal Investigator
NYP/Weill Cornell Medical Center
New York New York, 10065, United States More Info
Site Public Contact
Contact
212-746-1848
Jia Ruan
Principal Investigator
University of Rochester
Rochester New York, 14642, United States More Info
Site Public Contact
Contact
585-275-5830
Paul M. Barr
Principal Investigator
Memorial Sloan Kettering Nassau
Uniondale New York, 11553, United States More Info
Site Public Contact
Contact
212-639-7592
Alison J. Moskowitz
Principal Investigator
Wilmot Cancer Institute at Webster
Webster New York, 14580, United States More Info
Site Public Contact
Contact
[email protected]
Paul M. Barr
Principal Investigator
UNC Lineberger Comprehensive Cancer Center
Chapel Hill North Carolina, 27599, United States More Info
Site Public Contact
Contact
877-668-0683
[email protected]
Anne W. Beaven
Principal Investigator
Wake Forest University Health Sciences
Winston-Salem North Carolina, 27157, United States More Info
Site Public Contact
Contact
336-713-6771
Mary B. Seegars
Principal Investigator
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati Ohio, 45219, United States More Info
Site Public Contact
Contact
513-584-7698
[email protected]
Tahir Latif
Principal Investigator
Ohio State University Comprehensive Cancer Center
Columbus Ohio, 43210, United States More Info
Site Public Contact
Contact
800-293-5066
[email protected]
Jonathan E. Brammer
Principal Investigator
Dayton Physician LLC-Miami Valley Hospital North
Dayton Ohio, 45415, United States
Greater Dayton Cancer Center
Kettering Ohio, 45409, United States More Info
Site Public Contact
Contact
937-528-2900
[email protected]
Howard M. Gross
Principal Investigator
University of Cincinnati Cancer Center-West Chester
West Chester Ohio, 45069, United States More Info
Site Public Contact
Contact
513-584-7698
[email protected]
Tahir Latif
Principal Investigator
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States More Info
Site Public Contact
Contact
405-271-8777
[email protected]
Taha Al-Juhaishi
Principal Investigator
University of Pennsylvania/Abramson Cancer Center
Philadelphia Pennsylvania, 19104, United States More Info
Site Public Contact
Contact
800-474-9892
Stefan K. Barta
Principal Investigator
Rhode Island Hospital
Providence Rhode Island, 02903, United States More Info
Site Public Contact
Contact
401-444-1488
Adam J. Olszewski
Principal Investigator
Medical University of South Carolina
Charleston South Carolina, 29425, United States More Info
Site Public Contact
Contact
843-792-9321
[email protected]
Irl B. Greenwell
Principal Investigator
Huntsman Cancer Institute/University of Utah
Salt Lake City Utah, 84112, United States More Info
Site Public Contact
Contact
888-424-2100
[email protected]
Harsh Shah
Principal Investigator
Norris Cotton Cancer Center-North
Saint Johnsbury Vermont, 05819, United States More Info
Site Public Contact
Contact
800-639-6918
[email protected]
Frederick Lansigan
Principal Investigator
FHCC South Lake Union
Seattle Washington, 98109, United States More Info
Site Public Contact
Contact
800-804-8824
Christina Poh
Principal Investigator
Fred Hutchinson Cancer Research Center
Seattle Washington, 98109, United States More Info
Site Public Contact
Contact
800-804-8824
Christina Poh
Principal Investigator
University of Washington Medical Center - Montlake
Seattle Washington, 98195, United States More Info
Site Public Contact
Contact
800-804-8824
Christina Poh
Principal Investigator
Providence Saint Mary Regional Cancer Center
Walla Walla Washington, 99362, United States More Info
Site Public Contact
Contact
509-897-5993
[email protected]
Alison K. Conlin
Principal Investigator
Marshfield Medical Center-EC Cancer Center
Eau Claire Wisconsin, 54701, United States More Info
Site Public Contact
Contact
800-782-8581
[email protected]
Bilal H. Naqvi
Principal Investigator
Gundersen Lutheran Medical Center
La Crosse Wisconsin, 54601, United States More Info
Site Public Contact
Contact
608-775-2385
[email protected]
Michael O. Ojelabi
Principal Investigator
University of Wisconsin Carbone Cancer Center
Madison Wisconsin, 53792, United States More Info
Site Public Contact
Contact
800-622-8922
[email protected]
Saurabh Rajguru
Principal Investigator
Marshfield Medical Center-Marshfield
Marshfield Wisconsin, 54449, United States More Info
Site Public Contact
Contact
800-782-8581
[email protected]
Bilal H. Naqvi
Principal Investigator
Marshfield Clinic-Minocqua Center
Minocqua Wisconsin, 54548, United States More Info
Site Public Contact
Contact
800-782-8581
[email protected]
Bilal H. Naqvi
Principal Investigator
Marshfield Medical Center-River Region at Stevens Point
Stevens Point Wisconsin, 54482, United States More Info
Site Public Contact
Contact
800-782-8581
[email protected]
Bilal H. Naqvi
Principal Investigator
Marshfield Medical Center - Weston
Weston Wisconsin, 54476, United States More Info
Site Public Contact
Contact
800-782-8581
[email protected]
Bilal H. Naqvi
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

170

Study ID:

NCT04803201

Recruitment Status:

Recruiting

Sponsor:


Alliance for Clinical Trials in Oncology

How clear is this clinincal trial information?

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