Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
The purpose of this study is to find out whether the combination treatment of romidepsin and oral azacytidine is safe and effective in patients with Peripheral T-Cell Lymphoma (PTCL). This study will compare the experimental combination treatment of romidepsin and oral azacytidine to single agent drugs already determined effective in patients with PTCL. For the purposes of this study, the single agent drugs already used to treat lymphoma are called investigator's choice (IC), meaning the investigator will choose which one of these drugs to administer. The IC drug options include romidepsin, belinostat, pralatrexate or gemcitabine given alone. Funding Source: FDA OOPD.
Full description
Peripheral T-Cell Lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma (NHL) originating from mature (or post-thymic or 'peripheral') T- lymphocytes and NK cells. They are considered very aggressive and are often resistant to conventional chemotherapy.
This study employs a stratified randomization with equal allocation within strata of patients to receive oral 5-azacytidine (AZA) plus romidepsin (ROMI) versus pre-specified investigator choice (ROMI, belinostat, pralatrexate or gemcitabine), for the treatment of relapsed or refractory (R/R) PTCL. The dose and schedule of AZA/ROMI has been determined from a phase I clinical trial of the combination. The primary objective of this study is to estimate the progression free survival (PFS) among patients receiving the combination compared to single agent of choice.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
Patients must have histologically confirmed relapsed or refractory peripheral T-cell lymphoma as defined by 2016 WHO criteria (Section 13.7), who have progressed following one line of prior systemic therapy.
Patients are required to have no more than 3 lines of prior therapy (with cytoreductive therapy [ex ICE, DHAP, etc.] followed by autologous stem cell transplant counting as one line of therapy). Patients are eligible if they have relapsed after prior autologous or allogeneic stem cell transplant.
Patients with anaplastic large cell lymphoma are required to have received brentuximab vedotin (Bv) prior to study enrollment.
Measurable Disease as defined in Section 8.1.3.1.
Age ≥18 years.
ECOG performance status ≤2
Patients must have adequate organ and marrow function as defined below:
Absolute neutrophil count (ANC): ≥1000/mm3 (≥1000/dL); Platelets: > 75,000/mm3; Serum Creatinine:< 2 x ULN OR creatinine clearance >50 mL/min/for patients with creatinine levels above ULN; Bilirubin: ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4x ULN is allowed); AST and ALT: ≤ 2 x ULN OR ≤ 3 X ULN in presence of demonstrable liver involvement; Serum potassium: ≥ 3.8 mmol/L; Serum magnesium≥1.8 mg/dL.
Negative urine or serum pregnancy test for females of childbearing potential
All females of childbearing potential and male subjects must agree to use an effective method of contraception (see section 5.4 for more details)
Be willing and able to provide written consent or assent for the trial.
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study:
Diagnosis of patch/plaque stage mycosis fungoides
Prior Therapy: Prior exposure to any hypomethylating agent or any histone deacetylase inhibitor (ex: romidepsin, chidamide, belinostat, or vorinostat); exposure to chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs.
No other concurrent investigational agents are allowed within 2 weeks of enrollment.
Known central nervous system metastases, including lymphomatous meningitis
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Nursing women
Other active concurrent malignancy (except non-melanoma skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast (DCIS or LCIS). If there is a history of prior malignancy, the patient must be disease-free for ≥ 3-years. Patients whose lymphoma has transformed from a less aggressive histology remain eligible.
Patients known to be Human Immunodeficiency Virus (HIV)-positive.
Patients with active Hepatitis A, hepatitis B, or hepatitis C infection.
Concomitant use of CYP3A4 inhibitors (see Section 13.3)
History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, 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 the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity
Abnormal coagulation parameters (PT >15 seconds, PTT>40 seconds, and/or INR >1.5) unless related to ongoing anticoagulation treatment required by the patient.
Known or suspected hypersensitivity to azacitidine (or any excipients in the formulation) or mannitol.
Any known cardiac abnormalities such as:
Primary purpose
Allocation
Interventional model
Masking
50 participants in 2 patient groups
Loading...
Central trial contact
Enrica Marchi, MD; Marian Abdelmalek, MS
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal