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

Active:	Yes
Cancer Type:	Hematopoietic Malignancies Lymphoma Non-Hodgkin Lymphoma Unknown Primary	NCT ID:	NCT04803201
Trial Phases:	Phase II	Protocol IDs:	A051902 (primary) A051902 NCI-2021-01380
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Alliance for Clinical Trials in Oncology
NCI Full Details:	http://clinicaltrials.gov/show/NCT04803201

Summary

This phase II trial studies the effect of adding duvelisib or CC-486 to the usual chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone vs. chemotherapy alone in treating patients with peripheral T-cell lymphoma. Duvelisib is in a class of medications called kinase inhibitors. It works by blocking the signals that cause cancer cells to multiply. This helps to stop the spread of cancer cells. Chemotherapy drugs, such as CC-486, cyclophosphamide, doxorubicin, vincristine, etoposide, 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. Prednisone is used to reduce inflammation and lower the body's immune response to help reduce the side effects of chemotherapy drugs. This trial will help to determine whether adding duvelisib or CC-486 to the usual chemotherapy is better than chemotherapy alone in treating peripheral T-cell lymphoma.

Objectives

PRIMARY OBJECTIVE:
I. To compare the complete remission (CR) rates by fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) using the Lugano 2014 criteria following completion of treatment with duvelisib-cyclophosphamide (C) doxorubicin (H) vincristine (O) (etoposide [E]) prednisone (P) versus (vs) CHO(E)P and with 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 CR rates by FDG PET/CT or CT alone using the Lugano 2014 criteria.
III. 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.
IV. To determine whether designation of follicular helper T-cell phenotype is correlated with response to therapy, PFS, EFS, and OS.
V. 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 (given only to patients =< 60 years old) IV on day 1 or days 1-3 or orally (PO) once daily (QD) on days 2-3, 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 (given only to patients =< 60 years old) IV on day 1 or days 1-3 or PO QD on days 2-3, 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 (given only to patients =< 60 years old) IV on day 1 or days 1-3 or PO QD on days 2-3, 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.

All patients undergo bone marrow biopsy during screening and on the trial. Patients also undergo positron emission tomography (PET)/ computed tomography (CT) throughout the trial. Additionally, patients undergo blood sample collection on the trial and during follow up.

After completion of study treatment, patients are followed up every 12 weeks for 2 years, every 24 weeks until 5 years 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.

Treatment Sites in Georgia

Emory Saint Joseph's Hospital
5665 Peachtree Dunwoody Road NE
Atlanta, GA 30342
www.emoryhealthcare.org

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
winshipcancer.emory.edu

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.