A Phase II Study of Plitidepsin in Patients with Angioimmunoblastic T-cell Lymphoma.

Phase 1

• Conditions: MedDRA version: 18.1Level: PTClassification code 10002453Term: Angioimmunoblastic T-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001909-14-ES
• Lead Sponsor: Pharma Mar, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-02-03
• Last Update Posted: 20 August 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

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 (< 5 × ULN if isolated ALP
increase, i.e., without ALT/AST or bilirubin increase).
g)Calculated creatinine clearance (CrCL) ? 30 mL/minute (Cockcroft-
Gault formula).
h)Creatine phosphokinase (CPK) ? 2.5 × ULN.
i)Albumin ? 2.5 g/dL.
8)Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or
multiple-gated acquisition scan (MUGA) above the lower limit of normal
(LLN) and not less than 45%.
* Patient inclusion can be approved based on local histopathological
report(s). Eligibility will be confirmed using diagnosis and/or relapse
biopsy specimens submitted for central pathological review prior to each
futility analysis/end of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

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).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified