A Study of Plitidepsin in Patients With Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma

NCT03070964 | Terminated Phase 2 Results DMC

• 1 other identifier: APL-B-021-13
• Study Type: interventional
• Target: 14
• Locations: 4 countries
• Sites: 17

Brief 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).

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate by the Lugano Classification Per Independent Review Assessment

  The study protocol established that the analysis of the primary endpoint should have been done once a total of 60 patients have received plitidepsin, with two futility analyses planned after the inclusion of approximately 15 and 30 patients, respectively. However, only a total of 14 patients were included, of whom 13 were treated, and 12 were evaluable for the primary efficacy endpoint (ORR per IRC in the "Per Protocol Patients" population). As a result of slow patient accrual, the study was closed before reaching the target enrollment of 15 patients for the first futility analysis, and the primary endpoint (ORR according to the Lugano classification criteria and per IRC) was not assessed.

  Change from Baseline to assessments at: 1/2 weeks after cycle 3 and 4-8 weeks after cycle 6 (1cycle =28days), follow-up every 4 months +/- 2 weeks until progression disease or end of study (expected: 42 months)

Secondary Outcomes (1)

• Overall Response Rate by Investigator's Assessment - Per Protocol Patients Population

  From the date when the remission criteria are fulfilled to the first date when progressive disease, recurrence or death (due to any cause)is documented, expected at a maximum of 42 months

Study Arms (1)

Plitidepsin

EXPERIMENTAL

Drug: plitidepsin

Interventions

plitidepsin DRUG

Also known as: APLD Aplidine

Plitidepsin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written informed consent of the patient (both to participate in the study and to provide biopsy samples) obtained before any study-specific procedure.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
• Life expectancy ≥ 3 months.
• Histologically confirmed diagnosis of R/R AITL (eligibility needs to be confirmed by central pathological review).
• 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).
• 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.
• Platelet count ≥ 75 × 109/L.
• Hemoglobin ≥ 9 g/dL. Patients may receive red blood cells (RBC) and/or erythropoietin (EPO) and/or platelet transfusions in accordance with institutional guidelines.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × the upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × ULN.
• Alkaline phosphatase (ALP) ≤ 3.0 × ULN (\< 5 × ULN if isolated ALP increase, i.e., without ALT/AST or bilirubin increase).
• Calculated creatinine clearance (CrCL) ≥ 30 mL/minute (Cockcroft-Gault formula).
• Creatine phosphokinase (CPK) ≤ 2.5 × ULN.
• Albumin ≥ 2.5 g/dL.

You may not qualify if:

• Prior treatment with plitidepsin.
• Concomitant diseases/conditions:
• History or presence of angina, myocardial infarction, clinically relevant valvular heart disease, uncontrolled hypertension, or congestive heart failure within the previous 12 months.
• Active uncontrolled infection. Active hepatitis B or C virus (HBV or HCV), or human immunodeficiency virus (HIV)infection.
• Morphological or cytological features of myelodysplasia and/or post chemotherapy aplasia on bone marrow (BM) assessment.
• 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).
• Limitation of the patient's ability to comply with the treatment or follow-up requirements.
• 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.
• Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
• Central nervous system (CNS) involvement.
• 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.
• 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.
• Major upper gastrointestinal bleeding episode occurring during the previous year before screening.
• Known hypersensitivity to any of plitidepsin's formulation components

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (17)

Northwestern University Medical School

Chicago, Illinois, 60611, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Faculty Hospital Ostrava

Ostrava, 708 52, Czechia

Location

Fakultni Nemocnice Praha

Prague, 100 34, Czechia

Location

Ospedale Clinico Aviano

Aviano, Pordenone, 33081, Italy

Location

Instituto di Ematologia "Seragnoli"

Bologna, 40138, Italy

Location

Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 119 - 129, Spain

Location

Centro Oncológico MD Anderson International España

Madrid, 28033, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, 07010, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Lymphoma

Interventions

plitidepsin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

On 14May18, Sponsor informed to the sites and IPs its decision to close the recruitment. Study was terminated before reaching the target enrollment due to slow patient accrual and the negative opinion of the EMA-refusal of the mark. auth. plitidepsin

Results Point of Contact

• Title: Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit.
• Organization: Pharma Mar, S.A.

clinicaltrials@pharmamar.com

+34 918466000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2017
• First Posted: March 6, 2017
• Study Start: October 25, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: October 14, 2020
• Results First Posted: October 14, 2020

Record last verified: 2020-09

Locations

IT (4); CZ (2); ES (9); US (2)