A Study of Plitidepsin in Patients With Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Immunoblastic Lymphadenopathy
Intervention: plitidepsin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Prospective, multicenter, phase II clinical trial to determine the efficacy of plitidepsin in
      patients with relapsed/refractory (R/R) angioimmunoblastic Tcell lymphoma (AITL).This is an
      international, multicenter study (with approximately 17 investigative sites).
    

Eligibility 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 study-specific 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):

               1. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L. Screening of ANC should be
                  independent of granulocytecolony stimulating factor (G-CSF) support for at least
                  one week and of pegylated G-CSF for at least two weeks.

               2. Platelet count ≥ 75 × 109/L.

               3. Hemoglobin ≥ 9 g/dL. Patients may receive red blood cells (RBC) and/or
                  erythropoietin (EPO) and/or platelet transfusions in accordance with
                  institutional guidelines.

               4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × the
                  upper limit of normal (ULN).

               5. Total bilirubin ≤ 1.5 × ULN.

               6. Alkaline phosphatase (ALP) ≤ 3.0 × ULN (< 5 × ULN if isolated ALP increase, i.e.,
                  without ALT/AST or bilirubin increase).

               7. Calculated creatinine clearance (CrCL) ≥ 30 mL/minute (Cockcroft-Gault formula).

               8. Creatine phosphokinase (CPK) ≤ 2.5 × ULN.

               9. Albumin ≥ 2.5 g/dL.

          8. Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple-gated
             acquisition (MUGA) scan within normal range (according to institutional standards).

        Exclusion Criteria:

          1. Prior treatment with plitidepsin.

          2. Concomitant diseases/conditions:

               1. History or presence of angina, myocardial infarction, clinically relevant
                  valvular heart disease, uncontrolled hypertension, or congestive heart failure
                  within the previous 12 months.

               2. 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.

               3. Active uncontrolled infection. Active hepatitis B or C virus (HBV or HCV), or
                  human immunodeficiency virus (HIV)infection.

               4. Morphological or cytological features of myelodysplasia and/or post chemotherapy
                  aplasia on bone marrow (BM) assessment.

               5. 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).

               6. Limitation of the patient's ability to comply with the treatment or follow-up
                  requirements.

               7. 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.

               8. Any other major illness that, in the Investigator's judgment, will substantially
                  increase the risk associated with the patient's participation in this study.

          3. Central nervous system (CNS) involvement.

          4. 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.

          5. 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.

          6. Major upper gastrointestinal bleeding episode occurring during the previous year
             before screening.

          7. Known hypersensitivity to any of plitidepsin's formulation components