Use of Venetoclax as Single Agent in Patients With Relapsed/Refractory BCL-2 Positive Peripheral T Cell Lymphoma

NCT03552692 | Terminated Phase 2 DMC

• 1 other identifier: FIL_VERT
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 13

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)

Conditions

T-Cell Lymphoma Relapsed; T-Cell Lymphoma Refractory

Keywords

BCL-2 positive; PTCL-NOS; angioimmunoblastic T-cell lymphoma (AITL); T-follicular helper origin (TFH); Venetoclax; single agent

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  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.

  After the first 3 cycles (each cycle is 28 days)

Secondary Outcomes (9)

• Complete remission (CR)

  After the first 3 cycles (each cycle is 28 days)

• Partial response (PR)

  After the first 3 cycles (each cycle is 28 days)

• Stable Desease (SD)

  After the first 3 cycles (each cycle is 28 days)

• Time To Response (TTR)

  1 year from the date of the first dose

• Duration of Remission (DoR)

  6 months from the first 3 cycles (each cycle is 28 days)

Study Arms (1)

ARM1 - Venetoclax (ABT-199)

EXPERIMENTAL

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.

Drug: Venetoclax

Interventions

Venetoclax DRUG

Venetoclax (ABT-199) will be administered orally (800 mg 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. Tumor Lysis Syndrome (TLS) is an important identified risk for Venetoclax in oncology studies. 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. to avoid TLS ABT-199 will be administered according the following ramp up: W eek 1 day 1: 20 mg W 1 day 2-3: 50 mg W 1 day 4-7: 100 mg W 2: 200 mg W 3: 400 mg W 4 and following: 800 mg

Also known as: ABT-199/GDC-0199

ARM1 - Venetoclax (ABT-199)

Eligibility Criteria

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

You may qualify if:

• Histologically documented diagnosis of BCL-2 positive PTCL-NOS, AITL, TFH as defined in the 2016 edition of the World Health Organization (WHO) classification. Only patients with percentage of BCL-2 positive tu-mor cells ≥ 25% in the relapse biopsy, if available, or otherwise in the ini-tial biopsy, will be included onto the study;
• Age ≥ 18 years
• Relapsed or refractory to at least one previous standard line of treatment
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
• At least one site of measurable nodal or extranodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan cannot be performed). Note: Patients with only bone marrow involvement are eligible
• Adequate hematological counts defined as follows:
• Absolute Neutrophil count (ANC) \> 1.0 x 10\^9/L unless due to bone marrow involvement by lymphoma
• Platelet count ≥ 50.000/mm\^3 unless due to bone marrow involvement by lymphoma
• Adequate renal function defined as follows:
• Creatinine clearance ≥ 30 mL/min
• Adequate hepatic function per local laboratory reference range as follows:
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN
• Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syn-drome or of non-hepatic origin)
• Subject understands and voluntarily signs an informed consent form ap-proved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific pro-cedures
• Subject must be able to adhere to the study visit schedule and other pro-tocol requirements

You may not qualify if:

• Histological diagnosis different from BCL-2 positive PTCL-NOS, AITL, and TFH
• Allogeneic or autologous stem cell transplant within 6 months prior to the informed consent signature
• Treatment with any of the following within 7 days prior to the first dose of study drug:
• steroid therapy for anti-neoplastic intent
• moderate or strong cytochrome P450 3A (CYP3A) inhibitors (see Ap-pendix C for examples)
• moderate or strong CYP3A inducers (see Appendix C for examples)
• Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug
• History of CNS involvement by lymphoma
• Administration or consumption of any of the following within 3 days prior to the first dose of study drug:
• grapefruit or grapefruit products
• Seville oranges (including marmalade containing Seville oranges)
• star fruit
• Previous treatment with a BCL-2 family protein inhibitor
• Subject is known to be positive for HIV (HIV testing is not required)
• Cardiovascular disease (NYHA class ≥2)

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (13)

Centro Riferimento Oncologico - S.O.C. Oncologia Medica A

Aviano, Italy

Location

Policlinico S.Orsola-Malpighi - Istituto di Ematologia "Seragnoli"

Bologna, Italy

Location

ASST Spedali Civili di Brescia - Ematologia

Brescia, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia

Milan, Italy

Location

Istituto Scientifico San Raffaele - Unità Linfomi - Dipartimento Oncoematologia

Milan, Italy

Location

AOU Maggiore della Carità di Novara - SCDU Ematologia

Novara, Italy

Location

IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia

Pavia, Italy

Location

Ospedale delle Croci - Ematologia

Ravenna, Italy

Location

Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia

Reggio Emilia, Italy

Location

Azienda sanitaria-universitaria integrata Trieste-SC Ematologia

Trieste, 34125, Italy

Location

Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - SOC Clinica Ematologica

Udine, Italy

Location

Ospedale di Circolo - U.O.C Ematologia

Varese, Italy

Location

ULSS 8 Berica - Ospedale S. Bortolo - Ematologia

Vicenza, Italy

Location

Related Publications (1)

• Ballotta L, Zinzani PL, Pileri S, Bruna R, Tani M, Casadei B, Tabanelli V, Volpetti S, Luminari S, Corradini P, Lucchini E, Tisi MC, Merli M, Re A, Varettoni M, Pesce EA, Zaja F. Venetoclax Shows Low Therapeutic Activity in BCL2-Positive Relapsed/Refractory Peripheral T-Cell Lymphoma: A Phase 2 Study of the Fondazione Italiana Linfomi. Front Oncol. 2021 Dec 6;11:789891. doi: 10.3389/fonc.2021.789891. eCollection 2021.

  PMID: 34938664 DERIVED

MeSH Terms

Conditions

Immunoblastic Lymphadenopathy

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Lymphadenopathy; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Francesco Zaja, MD

  Azienda Sanitaria Universitaria Integrata di Trieste

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Study design 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.

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: June 12, 2018
• Study Start: September 25, 2018
• Primary Completion: March 4, 2020
• Study Completion: February 17, 2023
• Last Updated: December 12, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (13)