Use of Venetoclax as Single Agent in Patients With Relapsed/Refractory BCL-2 Positive Peripheral T Cell Lymphoma
- Conditions
- T-Cell Lymphoma RefractoryT-Cell Lymphoma Relapsed
- Interventions
- Registration Number
- NCT03552692
- Lead Sponsor
- Fondazione Italiana Linfomi - ETS
- Brief Summary
The FIL_VERT study is a phase II, open label, multicenter clinical trial. The primary of objective of the Study is to evaluate the efficacy of Venetoclax ABT-199/GDC-0199) in terms of overall response rate (ORR) in patients with relapsed/refractory BCL-2 positive peripheral T cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and other nodal T-cell lymphomas of T-follicular helper origin (TFH)
- Detailed Description
This is an open-label, multi-center, single arm phase II trial, with a two-stage design, to evaluate the activity and safety of ABT-199 single agent in patients with BCL-2 pos R/R PTCL-NOS, AITL, TFH.
A pre-screening evaluation of immunohistochemical positivity of BCL-2 will be performed in the relapse biopsy, if available, or otherwise in the initial biopsy. BCL-2 evaluation will be centralized (FIL Laboratories). Only patients with a percentage of BCL-2 positive tumor cells ≥ 25% will be included onto the study. Patients will receive ABT-199 until disease progression, unacceptable toxicity, withdrawal of consent and/or the investigator determines that further therapy is not in the patient's best interest. The primary objective of the study is ORR which will be evaluated after 3 cycles of treatment.
ABT-199 will be administered orally at the dose of 800 mg once daily. Patients will receive ABT-199 until disease progression, unacceptable toxicity, withdrawal of consent and/or the investigator determines that further therapy is not in the patient's best interest (e.g., due to non-compliance, toxicity...) Response evaluation will be performed initially after 3 cycles from the beginning of treatment with ABT-199 (Response Assessment 1) and then every 3 cycles during the first 12 cycles, every 4 cycles from cycle 13 to 24; for those patients still on therapy after 24 cycles, the response evaluation, after this time, will be performed every 6 cycles.
Response will be evaluated according to the Lugano 2014 classification.
TLS is an important identified risk for ABT-199 in oncology studies, especially in CLL. Since there are no available data on the risk of TLS in PTCL, the risk of TLS development should be closely monitored during the study.
TLS prophylaxis includes:
1. ABT-199 will be administered according the following ramp up:
* week 1 day 1: 20 mg
* week 1 day 2-3: 50 mg
* week 1 day 4-7: 100 mg
* week 2: 200 mg
* week 3: 400 mg
* week 4 and following: 800 mg
2. Hospitalization and monitoring of the subject should occur for a minimum of 72 hours after the initial dose. Discharge of the subject is dependent upon review of chemistry labs 72 hours after the first dose of ABT-199
3. IV hydration (150 cc/hr, as tolerable) must be started upon admission and continued during hospitalization at least for 72 hours after the initial dose of ABT-199. Urine output must be monitored
4. Allopurinol 300 mg daily to be initiated 3 days before treatment and continued for up to 5 weeks based on the ongoing risk of TLS development. Subjects allergic to allopurinol must use another anti-hypeuricemic drug. Consider use of rasburicase if subjects baseline uric acid level is elevated
5. The investigator decision to proceed with ABT-199 treatment initiation and subsequent ramp up will be after having evaluated the normal value of the following biochemistry (potassium, uric acid, phosphorus, calcium and creatinine).
Biohemistry labs (potassium, uric acid, phosphorus, calcium and creatinine) must be performed as follow:
* week 1 (ABT-199 dose from 20 to 100 mg/daily): at timepoints 0 (pre-dose, within 4 hours from ABT-199 administration), 6-8, 24, 48, 72, 96 hours after the first dose of ABT-199. Day 2 dose should not be administered until the 24 hours post-dose labs are reviewed by the investigator;
* week 2 (ABT-199 dose 200 mg/daily): at timepoints 0 (pre-dose, with-in 4 hours from ABT-199 administration), 6-8, 24 hours after. Day 2 dose should not be administered until the 24 hours post-dose labs are reviewed by the investigator;
* week 3 (ABT-199 dose 400 mg/daily): at timepoints 0 (pre-dose, with-in 4 hours from ABT-199 administration), 6-8, 24 hours after. Day 2 dose should not be administered until the 24 hours post-dose labs are reviewed by the investigator;
* week 4 (ABT-199 dose 800 mg/daily): at timepoints 0 (pre-dose, with-in 4 hours from ABT-199 administration), 6-8, 24 hours after. Day 2 dose should not be administered until the 24 hours post-dose labs are reviewed by the investigator Nephrology (or other acute dialysis service) must be consulted/contacted on admission (per institutional standards to ensure emergency dialysis is available).
The efficacy interim analysis will be performed after enrollment of 18 patients. It is to be planned a stop in recruitment of at least 3 months to have the results of response assessment. The primary efficacy analysis will consist of an estimate of ORR on the efficacy population after the first 3 cycles of therapy, with 90% confidence intervals (according to 1-sided alpha error of 0.05). To proceed to the second stage, the minimum number of patients with an ORR is 3/18.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 22
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ARM1 - Venetoclax (ABT-199) Venetoclax Venetoclax (ABT-199) will be administered orally at the dose of 800 mg once daily. Response evaluation will be performed initially after 3 cycles from the beginning of treatment with ABT-199 and then every 3 cycles during the first 12 cycles, every 4 cycles from cycle 13 to 24; for those patients still on therapy after 24 cycles, the response evaluation, after this time, will be performed every 6 cycles.
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) After the first 3 cycles (each cycle is 28 days) Overall response rate (ORR) will be defined as the proportion of patient in CR or PR according to Re-sponse Criteria (Lugano 2014) after the first 3 cycles. Efficacy will be assessed after the first 3 cycles or, in case of discontinuation, at the EoT visit. Patients without response assessment (due to whatever reason) will be considered as non-responders.
- Secondary Outcome Measures
Name Time Method Partial response (PR) After the first 3 cycles (each cycle is 28 days) PR rate will be defined according to Lugano criteria21 after the first 3 cycles and at each restaging. The best overall response will be defined as the best response between the date of begin-ning of therapy and the last restaging. Patients without response assessment (due to whatever rea-son) will be considered as non-responders.
Time To Response (TTR) 1 year from the date of the first dose TTR will be defined for all patients who achieved a response (CR or PR) and is measured from the date of beginning of therapy until the date of response. Patients in relapse or progression will be cen-sored at their last assessment date. Patients death due to any cause will be consider censored or competing event according to different analysis plan
Stable Desease (SD) After the first 3 cycles (each cycle is 28 days) SD rate will be defined according to Lugano criteria21 after the first 3 cycles and at each restaging. The best overall response will be defined as the best response between the date of begin-ning of therapy and the last restaging. Patients without response assessment (due to whatever rea-son) will be considered as non-responders.
Duration of Remission (DoR) 6 months from the first 3 cycles (each cycle is 28 days) DoR will be defined for all patients who achieved a response (CR or PR) and it is measured from the time of response until the date of progression or relapse. Patients without relapse or progression will be censored at their last assessment date; Patients death due to any cause will be consider censored or competing event according to different analysis plan;
Overall Survival (OS) 1 year from the date of the first dose OS will be defined as the time from beginning of therapy until death as a result of any cause; patients alive will be censored at their last assessment date;
Duration of treatment (DoT) 1 year from the date of the first dose Duration of treatment (DoT) will be defined as the time from beginning of therapy until ABT-199 dis-continuation due to any reason;
Complete remission (CR) After the first 3 cycles (each cycle is 28 days) CR rate will be defined according to Lugano criteria21 after the first 3 cycles and at each restaging. The best overall response will be defined as the best response between the date of begin-ning of therapy and the last restaging. Patients without response assessment (due to whatever rea-son) will be considered as non-responders
Progression free Sruvival (PFS) 1 year from the date of the first dose PFS will be defined as the time from beginning of therapy until lymphoma relapse or progression or death as a result of any cause; responding patients and patients who are lost to follow up will be cen-sored at their last assessment date;
Toxicity - Incidence of Adverse Events Through study completion, up to 30 months Safety of ABT-199 in terms of relevant toxicity and of overall toxicity (as acute and long-term toxicity). Toxicity will be classified according to definitions of Common Terminology Criteria for Adverse Event version 4.03 (CTCAE) commencing during and up to 24 hours after the first drug infusion and at any time during therapy and follow-up.
Trial Locations
- Locations (13)
Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - SOC Clinica Ematologica
🇮🇹Udine, Italy
Centro Riferimento Oncologico - S.O.C. Oncologia Medica A
🇮🇹Aviano, Italy
ASST Spedali Civili di Brescia - Ematologia
🇮🇹Brescia, Italy
ULSS 8 Berica - Ospedale S. Bortolo - Ematologia
🇮🇹Vicenza, Italy
Azienda sanitaria-universitaria integrata Trieste-SC Ematologia
🇮🇹Trieste, Italy
Istituto Scientifico San Raffaele - Unità Linfomi - Dipartimento Oncoematologia
🇮🇹Milano, Italy
AOU Maggiore della Carità di Novara - SCDU Ematologia
🇮🇹Novara, Italy
IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia
🇮🇹Pavia, Italy
Ospedale delle Croci - Ematologia
🇮🇹Ravenna, Italy
Policlinico S.Orsola-Malpighi - Istituto di Ematologia "Seragnoli"
🇮🇹Bologna, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia
🇮🇹Milano, Italy
Ospedale di Circolo - U.O.C Ematologia
🇮🇹Varese, Italy
Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia
🇮🇹Reggio Emilia, Italy