Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma. MedDRA version: 18.1 Level: PT Classification code 10002453 Term: Angioimmunoblastic T-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Aplidin
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
INN or Proposed INN: plitidepsin
Other descriptive name: PLITIDEPSIN
Concentration unit: mg mill
Sponsors
Pharma Mar, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Voluntary written informed consent of the patient (both to participate in the study and to provide biopsy samples) obtained before any studyspecific procedure. 2)Age ? 18 years. 3)Eastern Cooperative Oncology Group (ECOG) performance status (PS) ? 2. 4)Life expectancy ? 3 months. 5)Histologically confirmed diagnosis of R/R AITL (eligibility needs to be confirmed by central pathological review.*) 6)At least a two-week washout period since the end of the last therapy (six weeks for a prior nitrosourea-containing regimen), recovery to grade ? 1 from any non-hematological adverse event (AE) derived from previous treatment (excluding alopecia). 7)Adequate bone marrow (BM), renal, hepatic, and metabolic function (assessed ? 14 days before inclusion in the study): a)Absolute neutrophil count (ANC) ? 1.0 × 109/L. Screening of ANC should be independent of granulocyte-colony stimulating factor (G-CSF) support for at least one week and of pegylated G-CSF for at least two weeks. b)Platelet count ? 75 × 109/L. c)Hemoglobin ? 9 g/dL. Patients may receive red blood cells (RBC) and/or erythropoietin (EPO) and/or platelet transfusions in accordance with institutional guidelines. d)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 3.0 × the upper limit of normal (ULN). e)Total bilirubin ? 1.5 × ULN. f)Alkaline phosphatase (ALP) ? 3.0 × ULN (=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: 1)Concomitant diseases/conditions: a)History or presence of angina, myocardial infarction, clinically relevant valvular heart disease, uncontrolled hypertension, or congestive heart failure within the previous 12 months. b)Symptomatic arrhythmia (excluding grade ? 2 anemia-related sinusal tachycardia) or any arrhythmia requiring ongoing treatment, and/or prolonged grade ? 2 QT-QTc, or presence of unstable atrial fibrillation. Patients with stable atrial fibrillation on treatment are allowed provided they do not meet any other cardiac or prohibited drug exclusion criterion. c)Active uncontrolled infection. Active hepatitis B or C virus (HBV or HCV), or human immunodeficiency virus (HIV) infection. d)Morphological or cytological features of myelodysplasia and/or postchemotherapy aplasia on BM assessment. e)Myopathy > grade 2 or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 × ULN in two different determinations performed one week apart). f)Limitation of the patient's ability to comply with the treatment or follow-up requirements. g)Diagnosis of another invasive malignancy unless free of disease for at least three years following therapy with curative intent. Patients with early-stage basal cell or squamous cell skin cancer, cervical intraepithelial neoplasia, cervical carcinoma in situ, or superficial bladder cancer, may be eligible to participate at the Investigator's discretion. h)Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study. 2)Central nervous system (CNS) involvement. 3)Women who are pregnant or breast feeding. Fertile patients (men and women) who are not using an effective method of contraception. All patients (men and women) must agree to use an effective contraceptive measure (if applicable) up to six months after treatment discontinuation. 4)Concomitant medications that include corticosteroids, chemotherapy, or other therapy that is or may be active against AITL, within the two weeks prior to treatment start. Concurrent corticosteroids are allowed, provided they are administered at an equivalent prednisone dose of ? 10 mg daily, as premedication for blood products only. 5)Major upper gastrointestinal bleeding episode occurring during the previous year before screening. 6)Known hypersensitivity to plitidepsin or any of its formulation components. A total of 60 patients with AITL confirmed by central pathological review are to be included in this study (unless one of the two planned futility analyses stops recruitment after the inclusion of approximately 15 and 30 patients).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of plitidepsin on the basis of overall response rate (ORR) in patients with relapsing/refractory angioimmunoblastic T-cell lymphoma (AITL).;Secondary Objective: ?To evaluate other efficacy endpoints (time-to-event parameters: duration of response [DoR], progression-free survival [PFS], PFS at 6/12 months [PFS6/PFS12], intrapatient PFS/TTP, overall survival [OS] and OS at 6/12 months [OS6/OS12]). ?To evaluate the safety profile of plitidepsin in this patient population. ?To characterize the pharmacokinetics (PK) of plitidepsin. ?To identify biomarkers that may be clinical endpoint surrogates for future plitidepsin studies or that may be predictive of plitidepsin activity.;Primary end point(s): Overall response rate (ORR), defined as the percentage of patients with remission, either complete (CR) or partial remission (PR), according to the Lugano classification response criteria per independent review. An external IRC will assign the objective response and a progression or censoring date for each patient according to a predefined algorithm provided in a separate charter.;Timepoint(s) of evaluation of this end point: During the Study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: During the study.;Secondary end point(s): *ORR per Investigator assessment (IA). *CR rate, defined as the percentage of patients with complete remission according to the Lugano classification per IRC and per IA. *Duration of response (DoR), defined as the time from the date when the remission criteria (PR or CR, whichever is first achieved) are fulfilled to the first date when PD, recurrence or death (due to any cause) is documented. Response will be assessed according to Lugano classification and per IRC and IA. *Progression-free survival (PFS), defined as the time from the date of first drug administration to the date of PD, death (of any cause), or last tumor evaluation per IRC and IA. *Progression-free survival at 6/12 months (PFS6/PFS12), defined as the Kaplan-Meier estimate of the percentage of patients who are progression-free at six/twelve months after the first drug administration per IRC and IA. *Intrapatient PFS/TTP, defined as the ratio of PFS achieved with the experimental treatment versus prior last TTP in the R/R setting. *Overall survival (OS), defined as the time from the date of the first dose to the date of death (of any cause) or last patient contact. *Overall survival at 6/12 months (OS6/OS12), defined as the Kaplan-Meier estimate of the percentage of patients who are alive at six/twelve months after first drug administration. *Treatment safety [AEs, serious adverse events (SAEs) and laboratory abnormalities] graded according to the NCI-CTCAE, v.4. Dose reductions, omitted doses or cycle delays due to treatment-related AEs, and reasons for treatment discontinuations will be analyzed. *Pharmacokinetics (PK), samples for PK analysis will be obtained during Cycle 1 exclusively. *Exploratory Biomarker Analysis, biopsy samples (initial and relapse) and blood samples will be analyzed in order to examine any correlation of efficacy with molecular markers related to the mechanism of action of plitidepsin or | — |
Countries
Czech Republic, Spain, Switzerland, United States
Contacts
Public ContactClinical Trials
Pharma Mar, S.A.
Outcome results
None listed