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

Learn more about:
Related Clinical Trial
A Phase 1, Study of CD4-Targeted Chimeric Antigen Receptor T-Cells (CD4- CAR-T) in Subjects With Relapsed or Refractory T-Cell Lymphoma CAR T-cells Against CD30 (HSP-CAR30) for Relapsed/ Refractory Hodgkin and T-cell Lymphoma. A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies A Clinical Trial of Chidamide Combined With Etoposide in Relapsed or Refractory NK/T-cell Lymphoma A Study of Evaluating the Safety and Efficacy of ATG-010 Combined With Chemotherapy Sequential With ATG-010 Monotherapy Maintenance in Peripheral T- and NK/T-cell Lymphoma Duvelisib Maintenance After Autologous Stem Cell Transplant in T-Cell and Indolent B-Cell Lymphomas Study of Brentuximab Vedotin as Therapy After Autologous Stem Cell Transplant in Cluster of Differentiation Antigen 30 (CD30) Positive Peripheral TCell Lymphomas AMG 319 Lymphoid Malignancy FIH Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation Palbociclib in Combination With Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL) PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies Tandem Auto-Allo Transplant for Lymphoma Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma Long-term Follow-up of Patients Treated With Autologous T Cells Genetically Modified Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) and Alemtuzumab for People With Refractory or Relapsed Chronic and Acute Adult T-cell Leukemia (ATL) Study of AZD5991 in Relapsed or Refractory Haematologic Malignancies. p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies Investigation of the Human Immune Response in Normal Subjects and Patients With Disorders of the Immune System and Cancer Study of IPI-145 in Combination With Rituximab or Bendamustine/Rituximab in Hematologic Malignancies A Phase II Study Of Imtox-25 In Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab in T- and NK-Cell Lymphomas CD4CAR for CD4+ Leukemia and Lymphoma Pembrolizumab for T/NK-cell lymphomasNK-cell Lymphomas Study of CHOP + Campath for T-Cell, Null Cell, or Natural Killer (NK)-Cell Lymphoma Anti-CD7 U-CAR-T Cell Therapy for T/NK Cell Hematologic Malignancies Safety and Efficacy Study of a Dual PI3K Delta/Gamma Inhibitor in Hematological Malignancies Dose Escalation Study of Clofarabine in Patients With Relapsed or Refractory Low Grade or Intermediate-Grade B-Cell Lymphoma Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma A Study for Patients With Non-Hodgkin’s Lymphomas High Risk Adult T-cell Leukemia/Lymphoma (ATLL-HR) and Allogeneic Transplant Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma CPI-613 in Combination With Bendamustine in Patients With Relapsed/Refractory T-Cell Non-Hodgkin Lymphoma Allo-HSCT as First-line Consolidation in High-risk PTCL A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL PD1 Combined With Apatinib in Patients With Relapsed or Refractory NK/T Cell Lymphoma Lenalidomide Therapy for Patients With Relapsed and/or Refractory, Peripheral T-Cell Lymphomas An Open Label, International, Multi-centre, Phase I/IIa Study of Lenalidomide (Revlimid) and Romidepsin (Istodax) for Relapsed /Refractory Hodgkin Lymphoma, Mature T-cell Lymphoma and Multiple Myeloma. (RId Study) A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low ( T-cell Brazil: Prospective Collection of Data in T-cell Lymphomas Patients A-dmDT390-bisFv(UCHT1) Immunotoxin Therapy for Patients With Cutaneous T-Cell Lymphoma (CTCL) Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Adult T Cell Lymphoma (ATL) Orally Fludarabine, Adriamycin and Dexamethasone (FAD) in Newly Diagnosed Peripheral T-cell Lymphomas (PTCL) ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas Phase I Dose-finding and Preliminary Efficacy Study of the Istodax® in Combination With Doxil® for the Treatment of Adults With Relapsed or Refractory Cutaneous T-cell Lymphoma Nivolumab in Combination With GDP/ L-asparaginase in NK/ T-cell Lymphoma Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas Helical Irradiation of Total Skin (HITS) for T Cell Lymphoma Efficacy of a Treatment With CHOP and Lenalidomide in First Line in Angioimmunoblastic T-cell Lymphoma (AITL) CD7 CAR-T Cells for Patients With R/R CD7+ NK/T Cell Lymphoma,T-lymphoblastic Lymphoma and Acute Lymphocytic Leukemia A Multicenter Clinical Trial of Daratumumab in Combination With Gemcitabine, Dexamethasone and Cisplatin in Patients With Relapsed/Refractory CD38 Positive PTCL-NOS, Angioimmunoblastic T-cell Lymphoma AITL and Other Nodal Lymphomas of T Follicular Helper Cells Origin Avelumab in Relapsed and Refractory Peripheral T-cell Lymphoma Use of Venetoclax as Single Agent in Patients With Relapsed/Refractory BCL-2 Positive Peripheral T Cell Lymphoma Efficacy and Safety Study of Fostamatinib Disodium Tablets to Treat T-Cell Lymphoma A Study of Improving the Efficacy of Treatment in High Risk T Cell Lymphoma Patients A Phase II Clinical Trial of Lenalidomide for T-cell Non-Hodgkin’s Lymphoma HuMax-CD4 in Non-Cutaneous T-Cell Lymphoma Gemcitabine in NK/T Cell Lymphoma A Pilot Study of Oncaspar® + Dexamethasone in Patients With Relapsed or Refractory T-Cell Lymphoma PD-1 Antibody, Chidamide, Lenalidomide and Etoposide for Relapsed or Refractory NK/T Cell Lymphoma Trial of Endostar Combined With CHOPT for T Cell Lymphoma Intratumoral Poly-ICLC Plus Low Dose Local Radiation in Low Grade Recurrent B and T Cell Lymphoma Study of Ibrutinib in Relapsed and Refractory T-cell Lymphoma A Dose Escalation Study Evaluating CPI-818 in Relapsed/Refractory T-Cell Lymphoma Endostar Combined With CHOP Regimen as First Line Chemotherapy for Peripheral T Cell Lymphoma LAMPP Trial for Peripheral and Cutaneous T-Cell Lymphoma LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma CD4 in Combination With CHOP in Treating Non-cutaneous Peripheral TCell Lymphoma Bendamustine in Patients With Refractory or Relapsed T-cell Lymphoma A Pilot Study of Sorafenib Examining Biomarkers in Refractory or Relapsed T-Cell Lymphoma Patients Safety and Efficacy of Tenalisib (RP6530) in Combination With Romidepsin in Patients With Relapsed/Refractory T-cell Lymphoma

Brief Title

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

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)

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall response rate (ORR)

Secondary Outcome

 Complete remission (CR)

Condition

T-Cell Lymphoma Relapsed

Intervention

Venetoclax

Study Arms / Comparison Groups

 ARM1 - Venetoclax (ABT-199)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

22

Start Date

September 25, 2018

Completion Date

December 2, 2022

Primary Completion Date

March 4, 2020

Eligibility 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Francesco Zaja, MD, , 

Location Countries

Italy

Location Countries

Italy

Administrative Informations


NCT ID

NCT03552692

Organization ID

FIL_VERT


Responsible Party

Sponsor

Study Sponsor

Fondazione Italiana Linfomi ONLUS


Study Sponsor

Francesco Zaja, MD, Principal Investigator, Azienda Sanitaria Universitaria Integrata di Trieste


Verification Date

November 2021