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LLPC Working Group


1. composition
2. goal
3. current studies
4. planned studies
5. closed studies

 


 

 


1. Composition:

Chair 
Prof. M.J. Kersten (AMC)

Vice-chair
Prof. M.C. Minnema (UMC Utrecht)
 

Secretary

Dr P. Mutsaers (ErasmusMC)


 

   


2. Goal:


The key objectives of this working group are:

The Lunenburg Lymphoma Phase I/II Consortium (LLPC) was founded in 2009 by six departments of Hematology of Dutch (academic) hospitals. The aim of the consortium is an active contribution to the implementation of so-called "first-in-man" / phase I-II studies in malignant hematological diseases . Initially the focus is on all subtypes of Non-Hodgkin lymphoma (B and T cell), Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL). Promising new agents can then be incorporated into phase III studies, housed in the HOVON Lymphoma and CLL Workgroups. In this way, HOVON contributes to frontline clinical research as regards the treatment of malignant lymphoma and CLL.

Secondly, the accumulated expertise can be used in conjunction with the respective HOVON Workgroups to promote HOVON first-in-man trials / phase I-II studies in other hematological malignancies.

So far, the studies are industry-sponsored trials. Ultimately, the goal is also to develop investigator-initiated studies. The working group will check every study that is offered by one of the members or by biotech-and pharmaceutical companies on relevance and feasibility. If it is decided to participate in the study, it will then be determined how many and which centers will participate.

At present, the participating hospitals are:
- Academic Medical Center (AMC), Amsterdam
- Erasmus Medical Center, Rotterdam
- University Medical Center Groningen (UMCG), Groningen
- Free University Medical Center (VUMC), Amsterdam
- University Medical Center Nijmegen (UMCN), Nijmegen 

- University Medical Center Utrecht (UMCU), Utrecht

- St. Antonius Hospital, Nieuwegein
- University Medical Center Leiden (LUMC), Leiden

- Maastricht University Medical Center (MUMC), Maastricht


  


3. Current studies:

 

  • ACT15320: A Phase 1/2 open-label, multi-center, safety, preliminary efficacy and pharmacokinetic (PK) study of isatuximab in combination with other anti-cancer therapies in participants with lymphoma. Open at MUMC. 

 

  • KTE-C19-107 (ZUMA-7): A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel versus Standard of Care Therapy in Subjects with Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7). Eligibility criteria can be found here. This study is open in AMC, UMCU, ErasmusMC and UMCG.

 

  • KTE-C19-103 (ZUMA-3): A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3) – The study is open in the AMC (m.j.kersten@amc.nl; hemat.trial@amc.nl), Erasmus MC (p.lugtenburg@erasmusmc.nl; p.mutsaers@erasmusmc.nl; researchverpleegkundige@erasmusmc.nl) and UMCG (t.van.meerten@umcg.nl). Eligibility criteria can be found here. Please contact the center if a patient is redirected for this study. A slot will be directly provided. Please note: ZUMA-3 (temporarily) closed for new patients!!!


  • JCAR017-BCM-001: A phase 2, single-arm, multi-cohort, multicenter trial to determine the efficacy and safety of JCAR017 in adult subjects with aggressive B-Cell non-Hodgkin lymphoma.
    The study is open at Erasmus MC (p.lugtenburg@erasmusmc.nl; p.mutsaers@erasmusmc.nl; researchverpleegkundigehematologie@erasmusmc.nl).
    Cohort 1: Subjects with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]) and follicular lymphoma Grade 3B (FL3B) per World Health Organization (WHO) 2016 classification (Swerdlow, 2016), after ≥ 2 lines of therapy, including an anthracycline and rituximab (or other CD20-targeted agent). Please inform first if a slot is available.
    In- and exclusion criteria can be found here. The study is temporary on hold

  


    • KTE-C19-101 (ZUMA-1): A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Subjects with Refractory Aggressive Non-Hodgkin Lymphoma (NHL) (ZUMA-1) – The study is open in the AMC and will be opened at the Erasmus MC, UMCG Groningen and UMCU Utrecht. Sites will be allocated slots according to the order of site activation. Eligibility criteria can be found here.  

     

    • CDK9: A Phase 1, Open-Label, Multicentre, Non-Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of AZD4573, a Potent and Selective CDK9 Inhibitor, in Subjects with Relapsed or Refractory Haematological Malignancies. The study is open in AMC and the Antonius Hospital Nieuwegein. In- and exclusion criteria can be found here.

     


     

     

     

    4. Planned studies:

    • TRANSFORM (Celgene JCAR017-BCM-003): a global randomized multicenter phase 3 trial to compare the efficacy and safety of JCAR017 to standard of care in adult subjects with high-risk, transplant-eligible relapsed or refractory aggressive B-cell non-Hodgkin lymphomas.
      The study will open at Erasmus MC (p.lugtenburg@erasmusmc.nl; p.mutsaers@erasmusmc.nl).


    • EDO-S101-1001: Phase 1study to investigate the safety, pharmacokinetic profiles and efficacy of EDO-S101(tinostamustine), a first-in-class alkylating histone deacetylase inhibition (HDACi) fusion molecule in relapsed/refractory hematological malignancies.
      The study will open at Erasmus MC, VUMC and LUMC.

     

    • ACT15320: A Phase 1/2 open-label, multi-center, safety, preliminary efficacy and pharmacokinetic (PK) study of isatuximab in combination with other anti-cancer therapies in participants with lymphoma.

     

  • CMAK638X2101: A phase I/II, multicenter, open-label study of MAK683 in adult patients with advanced   malignancies, hematological malignancies include relapsed or refractory DLBCL or FL with or without EZH2 mutation and relapsed or refractory T-cell lymphoma

     

     

  • Amgen 20150290: Phase 1b/3 study with blinatumumab and pembrolizumab treatment in 3th line DLBCL.
    The study will open at Erasmus MC, VUMC, LUMC, St Antonius Nieuwegein and UMCN.

  • NP39461: Open-label, dose escalation/expansion phase IB study to evaluate the safety, pharmacokinetics, and clinical activity of the combination of RO6870810 and venetoclax, with or without rituximab, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Protocol synopsis + eligibility criteria can be found here.
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    5. Closed studies:

     

    • CB103-C-101: A Phase I/IIA, Multi-Centre, Open-Label, Dose-Escalation Study with Expansion Arms to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CB-103 Administered Orally in Adult Patients with Advanced or Metastatic Solid Tumours and Haematological Malignancies Characterised by Alterations of the NOTCH Signalling Pathway
      In- and exclusion criteria can be found here. This study has been closed for hematological patients (03JUL2019)
    • KTE-C19-102 (ZUMA-2): A Phase 2 Multi-Center Study Evaluating the Efficacy of KTE-C19 in Subjects with Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2) – The study is open in the AMC (m.j.kersten@amc.nl; hemat.trial@amc.nl) Erasmus MC (p.lugtenburg@erasmusmc.nl; p.mutsaers@erasmusmc.nl; researchverpleegkundige@erasmusmc.nl) and UMCG (t.van.meerten@umcg.nl). Eligibility criteria can be found here.
      Zuma-2 is per 30JUN2019 closed for new patients

     

    •   SADAL trial, Protocol KCP-330-009; A Phase-2b Open-label, randomized Two-arm Study comparing high and low doses of selinexor (KPT-330) in patients with relpased/refractory Diffuse large B-cell Lymphoma (DLBCL). 

     

     

  • Attention: the study is not open anymore for diffuse large B cell lymphoma as of august 2016

     

  • JAVELIN DLBCL: Phase IB/phase 3 multicenter study of avelumab (MSB0010718C) in combination regimens that include an immune agonist, epigenetic modulator, CD20 antagonist and/or conventional chemotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
    The study will open at Erasmus MC (Rotterdam) , UMCN (Nijmegen) and LUMC (Leiden)

     

     

  • MEDI4736-NHL-001 A phase 1-2, open label, multicenter study to assess the safety and tolerability of Durvalumab (Anti-PD-L1 antibody) as monotherapy and in combination therapy in subjects with lymphoma and chronic lymphocytic leukemia

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  • - CUDC-907-201: Open label, phase 2 study to evaluate the efficacy and safety of CUDC-907 with and without rituximab in patients with relapsed/refractory MYC-altered diffuse large B-cell lymphoma

     

    - BMS, CHECKMATE CA209-139: A Single-Arm, Open-Label Phase 2 Study of Nivolumab (BMS-936558) in Subjects with Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) After Failure of Autologous Stem Cell Transplant (ASCT) Nivolumab is a fully human, IgG4 kappa isotype mAb that binds PD-1 on activated
    immune cells and disrupts engagement of the receptor with its ligands PD-L1 and PD-L2, thereby abrogating inhibitory signals and augmenting the host antitumor response. 


    - BMS CA-209-205 study
    ;

    A non-comparative, open-label, Phase 2 study with two cohorts, one treatment group with nivolumab (BMS-936558) in subjects with classical Hodgkin lymphoma (classical Hodgkin's Lymphoma, cHL) after failure of autologous stem cell transplantation (ASCT)

    - Novartis COEB071X2103 study
    Oral Protein Kinase C inhibitor AEB071 plus Oral mTOR inhibitor Everolimus. Phase Ib/II study in patients with relapse/refractory ABC subtype DLBCL or CD79-mutant DLBCL. 

    - Genentech DCS4968g: anti-CD79b-MMA / E iv, phase I / II study in relapsed / refractory B-cell NHL / CLL (mantle cell lymphoma excluded). 

    - Kirin Pharma, Protocol 0761-007: A Phase II study of the anti-CCR4 monoclonal antibody i.v. in pre-treated patients with peripheral T-cell lymphoma (PTCL).

    - Novartis HCD122/Lucatumumab in CD40 + follicular lymphoma refractory to Rituximab


    - Novartis-COEB071X2101 study (Protein Kinase C inhibitor, oral): A phase I dose-escalation study in patients with CD79 mutant DLBCL.

    - Romulus/Genentech, study GO27834; a randomized phase II study in which anti-CD79b-MMA / E + Rituximab is compared with anti-CD22-MMA / E + Rituximab in patients with relapsed or refractory follicular NHL or diffuse large B-cell lymphoma.

    - Sanofi Aventis ARD12130 (combined PI3K/mTOR inhibitor, oral): A phase II study in patients with relapsed / refractory mantle cell lymphoma, follicular lymphoma, CLL or small lymphocytic lymphoma.

    - Gilead Protocol GS-US-315-0102: GS-9820 orally, phase I dose-escalation study (PI3 kinase inhibitor, orally) in patients with relapsed / refractory indolent B-cell NHL, diffuse large B-cell lymphoma, mantle cell lymphoma, Hodgkin lymphoma or CLL

    - ACE WM-001; A Multicenter Open-label, Phase 1b Study of ACP-196 in Subjects with Waldenström Macroglobulinemia. 

    - ACE LY-004; An Open-label, Phase 2 Study of ACP-196 in Subjects with Mantle Cell Lymphoma

    - MSD, MK-3475-087 study; A Phase II clinical trial of MK-3475 (pembrolizumab) in subjects with relapsed or refractory (R/R) classical Hodgkin Lymphoma (cHL)

    - GO29365; a multicenter, open-label, phase 2 study of polatuzumab vendotin in combincation with bendamustine and rituximab versus bendamustine and rituximab in relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma

     

    - CARINA (Protocol 54767414LYM2001); An open label, Phase 2 Study to Evaluate Efficacy and Safety of Daratumumab in Relapsed or Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma

     

    - GO27878 study (Cavalli study): A phase IB/II, open-label study evaluating the safety and pharmacokinetics of GDC-0199 (ABT-199) in combination with rituximab (R) or Obinutuzumab (G) plus cyclofosfamide, doxorubicin, vincristine and prednisone (CHOP) in patients with B-cell Non-Hodgkin’s lymphoma (NHL) and DLBCL 

    - Transplant BRaVE study: Phase I/II feasibility study combining Brentuximab Vedotin with second line salvage chemotherapy (DHAP) in Hodgkin lymphoma patients refractory to first line chemotherapy or in first relapse who are eligible for high dose treatment followed by autologous peripheral blood stem cell transplantation