A Study of Plitidepsin in Patients With Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT03070964|
Recruitment Status : Terminated (The main reason that motivated the study termination was the slow recruitment of the trial.)
First Posted : March 6, 2017
Last Update Posted : July 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: plitidepsin||Phase 2|
Prospective, multicenter, phase II clinical trial to determine the efficacy of plitidepsin in patients with relapsed/refractory (R/R) AITL. The primary endpoint will be overall response rate (ORR) according to the Lugano classification response criteria per independent review.
Medical specialists (radiologists and hematologists) who are directly involved in the care of patients with AITL (but are not participating in this trial as investigators) will review all efficacy data (including radiological assessments, bone marrow biopsies) and will assign the best response and the date of objective response or progression/censoring according to their independent evaluation.
Central pathological review of each patient's original diagnosis report(s) will be required before inclusion.
Two futility analyses of the primary endpoint (ORR according to the Lugano classification criteria and per Independent Review Committee (IRC)) are planned around six months after approximately 25% and 50% of eligible patients (i.e., 15 and 30 patients respectively with AITL confirmed by central pathological review) have been treated. Two or less responders out of 15 patients or seven or less responders out of 30 patients, according to boundaries and sample size assumptions, will mean that the alternative hypothesis could be rejected, and thus recruitment might be stopped at the time of the first or second futility analysis, respectively. Otherwise, accrual will continue to 60 patients with AITL confirmed by central pathological review. This decision will be taken at the time by an Independent Data Monitoring Committee (IDMC). The IDMC, which will include specialists in peripheral T-cell lymphomas (PTCL) supported by a medical statistician, will review data provided by the Investigators, the IRC efficacy assessments and safety information and will advise whether the study should continue. Recruitment can continue during the review period.
If there are 19 or more responders of 60 patients, the efficacy of plitidepsin will be considered as clinically relevant in AITL patients.
Central pathological review will be conducted by experienced pathologists appointed by the Sponsor and available to the investigative sites for consultation about AITL diagnosis confirmation. Central pathological review is required for (a) local histopathology reports prior to patient treatment, and (b) tumor samples before each futility analysis and at the end of the study.
The central laboratory pathologists will be responsible for (a) approving patient inclusion on the basis of investigative site pathology reports provided during screening, (b) analyzing tumor biopsies (initial diagnosis and/or relapses) to confirm the AITL diagnosis, and (c) analyzing blood samples to identify plasma biomarkers and extract DNA.
Tumor samples (initial diagnosis and relapses) are required for central review to confirm AITL diagnosis but not to approve inclusion. Archived tissue samples of representative tumors must be sent for central review and biomarker analysis. If the diagnosis biopsy is not available (because the patient was diagnosed at another site, for example), the most recent representative biopsy (relapse and/or progression) will be used. Submitting both, however, is strongly recommended. Tumor blocks will be returned to the centers.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Plitidepsin in Patients With Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma|
|Actual Study Start Date :||November 2016|
|Actual Primary Completion Date :||July 2018|
|Actual Study Completion Date :||July 2018|
Other Name: APLD Aplidine
- Efficacy of plitidepsin on the basis of overall response rate (ORR) in patients with relapsing/refractory angioimmunoblastic Tcell lymphoma (AITL) [ Time Frame: 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) ]
- Duration of response (DoR) [ Time Frame: 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 ]
- Progression-free survival (PFS) [ Time Frame: 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 ]
- Overall Survival (OS) [ Time Frame: 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070964