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Trial record 8 of 129 for:    Venetoclax AND Relapsed

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

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ClinicalTrials.gov Identifier: NCT03552692
Recruitment Status : Recruiting
First Posted : June 12, 2018
Last Update Posted : February 7, 2019
Sponsor:
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS

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)

Condition or disease Intervention/treatment Phase
T-Cell Lymphoma Relapsed T-Cell Lymphoma Refractory Drug: Venetoclax Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open Label, Multicenter Trial of Venetoclax (ABT-199/GDC-0199) as Single Agent 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)
Actual Study Start Date : September 25, 2018
Estimated Primary Completion Date : November 15, 2019
Estimated Study Completion Date : November 15, 2020


Arm Intervention/treatment
Experimental: ARM1 - Venetoclax (ABT-199)

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

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

Other Name: ABT-199/GDC-0199




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 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 :
  1. Complete remission (CR) [ Time Frame: 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

  2. Partial response (PR) [ Time Frame: 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.

  3. Stable Desease (SD) [ Time Frame: 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.

  4. Time To Response (TTR) [ Time Frame: 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

  5. Duration of Remission (DoR) [ Time Frame: 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;

  6. Progression free Sruvival (PFS) [ Time Frame: 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;

  7. Overall Survival (OS) [ Time Frame: 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;

  8. Duration of treatment (DoT) [ Time Frame: 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;

  9. Toxicity - Incidence of Adverse Events [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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
  • Subject must be able to swallow capsules or tablets
  • Life expectancy ≥ 3 months
  • Women must be:
  • postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months)
  • surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),
  • completely abstinent (periodic abstinence from intercourse is not per-mitted) or if sexually active, be practicing a highly effective method of birth control (e.g., prescription oral contraceptives, contraceptive injec-tions, contraceptive patch, intrauterine device, double barrier method (e.g.: condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, be-fore entry, and must agree to continue to use the same method of con-traception throughout the study. They must also be prepared to contin-ue birth control measures for at least 1 month after terminating treat-ment.
  • women of childbearing potential must have a negative pregnancy test at screening
  • Men must agree to use an acceptable method of contraception (fort themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 1 month after receiving the last dose of study drug.

Male even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following:

  • practice effective barrier contraception during the entire study treatment period and through 1 months after the last dose of study drug, or
  • agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods for the female part-ner] and withdrawal are not acceptable methods of contraception)

Exclusion criteria

  • 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)
  • Creatinine Clearance < 30 mL/min
  • Significant history of neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.
  • Any history of other active malignancies within 3 years prior to study en-try, with the exception of adequately treated in situ carcinoma of the cer-vix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, previous malignancy confined and surgically re-sected with curative intent.
  • Subject who has malabsorption syndrome or other condition which pre-cludes enteral route of administration.
  • Evidence of other clinically significant uncontrolled condition(s) including, but not limited to uncontrolled and/or active systemic infection (viral, bac-terial or fungal)
  • Active HBV positive hepatitis
  • The following categories of patients HBV positive but with non evidence of active hepatitis may be considered for the study:
  • HBsAg positive with HBV DNA < 2000 UI/ml (inactive carriers); HBV DNA > 2000 UI/ml is criteria of exclusion
  • HBsAg negative but HBsAb positive
  • HBsAg negative but HBcAb positive
  • Patients HBsAg positive with HBV DNA < 2000 UI/ml and HBsAg nega-tive but HBcAb positive will be eligible for the study only if they accept to receive prophylactic Lamivudine 100 mg/daily for all the period of treatment and at least for 12 months after the end of therapy. Treatment with ABT-199 should be stopped in case of hepatitis reactivation.
  • Active HCV positive hepatitis
  • If female, the patient is pregnant or breast-feeding.

Information from the National Library of Medicine

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): NCT03552692


Contacts
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Contact: Emanuela Pesce +0039 059 4222577 epesce@filinf.it
Contact: Elena Borgo +0039 0131206288 eborgo@filinf.it

Locations
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Italy
A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C. Ematologia Not yet recruiting
Alessandria, Italy
Contact: Manuela Zanni, MD       manuela.zanni@ospedale.al.it   
Principal Investigator: Manuela Zanni, MD         
Università Politecnica delle Marche - Clinica di Ematologia Not yet recruiting
Ancona, Italy
Contact: Attilio Olivieri, MD       a.olivieri@univpm.it   
Principal Investigator: Attilio Olivieri, Prof.         
Centro Riferimento Oncologico - S.O.C. Oncologia Medica A Recruiting
Aviano, Italy
Contact: Michele Spina, MD       mspina@cro.it   
Principal Investigator: Michele Spina, MD         
Policlinico S.Orsola-Malpighi - Istituto di Ematologia "Seragnoli" Recruiting
Bologna, Italy
Contact: Pier Luigi Zinzani, MD       pierluigi.zinzani@unibo.it   
Principal Investigator: Pier Luigi Zinzani, MD         
ASST Spedali Civili di Brescia - Ematologia Not yet recruiting
Brescia, Italy
Contact: Alessandro Re, MD       alessandro.re@asst-spedalicivili.it   
Principal Investigator: Alessandro Re, MD         
Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia Not yet recruiting
Firenze, Italy
Contact: Luigi Rigacci, MD       luigi.rigacci@unifi.it   
Principal Investigator: Luigi Rigacci, MD         
Ospedale Policlinico San Martino S.S.R.L. - IRCCS per l'Oncologia - Ematologia Not yet recruiting
Genova, Italy
Contact: Angela Congiu, MD       angelagiovanna.congiu@hsanmartino.it   
Principal Investigator: Angela Congiu, MD         
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia Not yet recruiting
Milano, Italy
Contact: Paolo Corradini, MD       paolo.corradini@unimi.it   
Principal Investigator: Paolo Corradini, MD         
Istituto Scientifico San Raffaele - Unità Linfomi - Dipartimento Oncoematologia Not yet recruiting
Milano, Italy
Contact: Andrés Ferreri, MD       andres.ferreri@hsr.it   
Principal Investigator: Andrés Ferreri, MD         
AOU Maggiore della Carità di Novara - SCDU Ematologia Not yet recruiting
Novara, Italy
Contact: Luca Nassi, MD       luca.nassi@med.uniupo.it   
Principal Investigator: Luca Nassi, MD         
A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia Not yet recruiting
Palermo, Italy
Contact: Caterina Patti, MD       k.patti@villasofia.it   
Principal Investigator: Caterina Patti, MD         
IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia Not yet recruiting
Pavia, Italy
Contact: Marzia Varettoni, MD       m.varettoni@smatteo.pv.it   
Principal Investigator: Marzia Varettoni, MD         
Ospedale delle Croci - Ematologia Recruiting
Ravenna, Italy
Contact: Monica Tani, MD       monica.tani@auslromagna.it   
Principal Investigator: Monica Tani, MD         
Azienda Unità Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia Not yet recruiting
Reggio Emilia, Italy
Contact: Francesco Merli, MD       merli.francesco@ausl.re.it   
Principal Investigator: Francesco Merli, MD         
Policlinico Umberto I - Università "La Sapienza" - Istituto Ematologia -Dipartimento di Biotecnologie Cellulari ed Ematologia Not yet recruiting
Roma, Italy
Contact: Maurizio Martelli, Prof.       martelli@bce.uniroma1.it   
Principal Investigator: Maurizio Martelli, MD         
A.O.U. Citta della Salute e della Scienza di Torino - S.C.Ematologia Not yet recruiting
Torino, Italy
Contact: Annalisa Chiappella, MD       achiappella@cittadellasalute.to.it   
Principal Investigator: Annalisa Chiappella, MD         
A.O. C. Panico - U.O.C Ematologia e Trapianto Not yet recruiting
Tricase, Italy
Contact: Vincenzo Pavone, MD       salentoematologia@piafondazionepanico.it   
Principal Investigator: Vincenzo Pavone, MD         
Azienda sanitaria-universitaria integrata Trieste-SC Ematologia Not yet recruiting
Trieste, Italy, 34125
Contact: Francesco Zaja, MD       francesco.zaja@asuits.sanita.fvg.it   
Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine) - SOC Clinica Ematologica Recruiting
Udine, Italy
Contact: Stefano Volpetti, MD       stefano.volpetti@asuiud.sanita.fvg.it   
Principal Investigator: Stefano Volpetti, Dr.         
Ospedale di Circolo - U.O.C Ematologia Recruiting
Varese, Italy
Contact: Michele Merli, MD       michelepavia@hotmail.com   
Principal Investigator: Michele Merli, MD         
ULSS 8 Berica - Ospedale S. Bortolo - Ematologia Recruiting
Vicenza, Italy
Contact: Carlo Visco, MD       carlo.visco@aulss8.veneto.it   
Principal Investigator: Carlo Visco, MD         
Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
Investigators
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Principal Investigator: Francesco Zaja, MD Azienda Sanitaria Universitaria Integrata di Trieste

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Responsible Party: Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier: NCT03552692     History of Changes
Other Study ID Numbers: FIL_VERT
First Posted: June 12, 2018    Key Record Dates
Last Update Posted: February 7, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fondazione Italiana Linfomi ONLUS:
BCL-2 positive
PTCL-NOS
angioimmunoblastic T-cell lymphoma (AITL)
T-follicular helper origin (TFH)
Venetoclax
single agent
Additional relevant MeSH terms:
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Venetoclax
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antineoplastic Agents