A Phase II Study of Duvelisib Maintenance After First-Line Therapy for Peripheral T-Cell Lymphoma
A Phase II Study of Duvelisib Maintenance After First-Line Therapy for Peripheral T-Cell Lymphoma
This phase II trial tests how well duvelisib works as treatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy (maintenance) for patients with peripheral T-cell lymphomas. 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.
PRIMARY OBJECTIVE:
I. Determine the efficacy of duvelisib maintenance therapy in peripheral T-cell lymphoma (PTCL) patients who have achieved a complete response (CR) following first-line treatment and are either ineligible for or decline consolidative autologous stem cell transplantation (ASCT).
SECONDARY OBJECTIVE:
I. Determine the tolerability and preliminary survival outcomes of duvelisib maintenance therapy.
EXPLORATORY OBJECTIVE:
I. Examine the association between biomarkers (e.g., minimal residual disease [MRD]) and clinical outcomes (overall response rate [ORR], progression free survival [PFS]).
OUTLINE:
Patients receive duvelisib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients who remain in continuous complete response may continue to receive duvelisib for an additional 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy during screening, as well as positron emission tomography (PET)/computed tomography (CT) scans and blood sample collection throughout the study. Patients may also undergo bone marrow aspiration and biopsy on study.
After completion of study treatment, patients are followed up at 4-6 weeks, then periodically for up to 5 years.
Inclusion Criteria:
Documented informed consent of the participant and/or legally authorized representative.
Age: ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) ≤ 2
Histologically confirmed nodal T-follicular helper (TFH) cell lymphomas or PTCL-not otherwise specified (NOS). Nodal TFH cell lymphomas encompass three subtypes:
Completion of first-line multi-agent chemotherapy with a cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-based regimen and documentation of complete response (CR) per Lugano criteria within the previous 6 months prior to enrollment. Prior corticosteroid monotherapy is not considered a line of therapy
Ineligible for or decline consolidative autologous stem cell transplantation. Ineligibility is defined by:
Patient deemed ineligible for high-dose chemotherapy and ASCT based on physician's assessment
AND at least one of the following criteria:
Recovery to ≤ grade 1 or baseline for any toxicities due to prior treatments, with the exception of peripheral neuropathy (recovery to ≤ grade 2) or alopecia
Platelets ≥ 25,000/mm^3
Hemoglobin ≥ 8 g/dL
CD4 lymphocyte count ≥ 50/mm^3 (0.05 × 10^9/L)
Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (in patients with Gilbert's Syndrome a bilirubin > 1.5 × ULN but ≤ 3 × ULN may be allowed with sponsor approval)
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) ≤ 2.5 × ULN
Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × ULN
Serum creatinine ≤ 2.0 × ULN or creatinine clearance ≥ 30 mL/min (estimated by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] or Cockcroft-Gault equation or measured)
Seronegative for HIV antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) OR patients with presence of hepatitis B core antibody (HBcAb), but absence of hepatitis B surface antigen (HBsAg), are eligible if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable (< 20 IU), and if they are willing to undergo monitoring every 4 weeks for HBV reactivation. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
Women of childbearing potential (WOCBP): negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test within 1 week before first treatment (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally postmenopausal for at least 12 consecutive months. Women who are considered not to be of childbearing potential are not required to have a pregnancy test
Agreement by females and males of reproductive potential (i.e., not surgically sterile or female patients who are not postmenopausal) must be willing to use a highly effective method of contraception for the duration of study treatment and for at least 1 months after the last dose of duvelisib
Exclusion Criteria:
Prior organ transplantation
Major surgery within 4 weeks prior to enrollment
Administration of a live vaccine within 30 days of cycle (C) 1 day (D) 1
Unable to receive prophylactic treatment for pneumocystis at enrollment
Use of medications or consumption of foods that are strong inducers or inhibitors of CYP3A must be discontinued at least 2 weeks prior to study intervention. Patients who (after enrollment) require use of a strong CYP3A4 inhibitor to treat a fungal/mold infection will require dose reductions
Known central nervous system involvement by PTCL
Patients with known diagnosis of
Active cytomegalovirus (CMV) infection (patients with detectable viral load)
History of tuberculosis treatment within 2 years prior to enrollment
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) which requires systemic treatment. Patients may proceed with screening during treatment for infection, but systemic treatment must be completed by cycle 1 day 1
History of cirrhosis or chronic alcohol abuse
Symptomatic inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of duvelisib
Concurrent active malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. The following are eligible without a specific waiver: nonmelanoma skin cancer, carcinoma in situ of the cervix
Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, such as pulmonary disease, including obstructive pulmonary disease and history of bronchospasm, uncontrolled diabetes, severe psychiatric disorder or unstable cardiac disease as defined by one of the following:
History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block
History of allergic reactions attributed to compounds of similar chemical or biologic composition to duvelisib
Participants who are receiving other investigational agents
Female patients who are breastfeeding
Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)