A051902 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
Investigating Treatment Options for Peripheral T-cell Lymphoma
Brief description of study
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 of study
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.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: 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
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Age: 18 years or above
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Gender: All
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
This study investigates the effects of adding investigational medications to the usual chemotherapy regimen for patients with peripheral T-cell lymphoma. The purpose of this study is to compare the effectiveness of three different treatment arms: one with the investigational medication duvelisib, another with the investigational medication CC-486, and the third with standard chemotherapy alone.
Participants in this study will be randomly assigned to one of the three treatment arms. In the first arm, patients will receive duvelisib along with chemotherapy drugs, including cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone. In the second arm, patients will receive CC-486 with the same chemotherapy drugs. The third arm will consist of the standard chemotherapy regimen without any additional investigational medication. The study will monitor the complete remission rates using imaging techniques such as PET/CT scans to assess the effectiveness of the treatments.
- Who can participate: Adults aged 18 and older with a confirmed diagnosis of peripheral T-cell lymphoma with less than 10% CD30 expression can participate. Participants must have measurable disease, no prior systemic therapy for lymphoma, and meet specific health criteria, including adequate blood counts and organ function.
- Study details: Participants will receive chemotherapy with or without investigational medications. The investigational medications include duvelisib and CC-486, which are being studied for their potential to improve treatment outcomes. Participants will be monitored for response to treatment and side effects.
Study is selecting its participants from a population, or group of people, decided on by the researchers in advance.
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