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Patients Against Lymphoma

 

Locate trials by Type of Agent 

Last update: 12/05/2014


Agents of special interest based on recent encouraging clinical reports

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ABT-199  (activating apoptosis) Find trials
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Adcetris ®  SGN-35 / brentuximab vedotin  (antibody-drug conjugate: anti-cd30 + antitubulin)  Find trials
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Belinostat PXD101 (epigenetic - recent approval) Find trials
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Cd19 CAR T-cell therapy (adoptive immunotherapy)  Find trials 
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GA-101 (Obinutuzumab), next generation cd20 antibody  Find trials
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Lenalidomide (immune modulation and direct activity)  Find trials
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Ibrutinib (all - recent approval for CLL; inhibiting b-cell receptor pathway) Find trials
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Ibrutinib for lymphoma only  Find Trials
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Idelalisib GS-1101 formerly CAL101 (inhibiting b-cell receptor pathway)  Find trials
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PD1/L antibodies (activates immune system - immune checkpoint blockade)  Find trials  (updated)
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Vidaza ®  5-Azacytidine (epigenetic - activating or shutting off genes) Find trials 


What's New

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Selinexor (KPT-330) lymphoma trial query - ClinicalTrials.gov http://1.usa.gov/1xs0cJv
ASH 2014: The Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Demonstrates Broad and Durable Clinical Activity in Relapsed / Refractory Non Hodgkin’s Lymphoma (NHL)
 
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Studies for peripheral t-cell lymphoma testing Brentuximab Vedotin - 
ClinicalTrials.gov http://1.usa.gov/1DGscZU

The ASCO Post
Brentuximab Vedotin Shows Antitumor Activity in Patients With Relapsed Peripheral T-Cell Lymphoma http://bit.ly/1G6asLx 

Among the 14 patients achieving an objective response, 8 had complete responses, including 5 patients with angioimmunoblastic T-cell lymphoma. At the time of the study report, the median duration of response for all patients was 7.6 months, with five responding patients remaining in follow-up and five on therapy.

This will lead to a study testing this agent as a part of first line therapy for this very challenging indication.  Query to locate such studies above.
 
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Testing APTO-253 HCl in Patients With Relapsed or Refractory Hematologic Malignancies http://1.usa.gov/1wFens8

Background from sponsor: http://aptose.com/apto-253/

APTO-253 is a novel small molecule with potent anti-tumor activity in cancer cells via tumor suppressor induction leading to cell cycle inhibition and programmed cell death. APTO-253 has been shown to induce the tumor suppressor gene Krüppel-like factor 4 (KLF4) and expression of p21, leading to cell cycle arrest and apoptosis. Nonclinical pharmacology studies have demonstrated that APTO-253 exerts in vivo anti-tumor activity in solid tumors and hematologic cancers. Aptose completed a Phase 1 study in patients with advanced or metastatic solid tumors in which promising clinical activity was observed.

 
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Testing PNT2258 (first-in-class DNAi ) for Pretreated Diffuse Large B-Cell Lymphoma (Wolverine) http://1.usa.gov/1x2Yy2I


ASH 2013: Paper: The BCL2 Targeted Deoxyribonucleic Acid Inhibitor (DNAi) PNT2258 Is Active In Patients With Relapsed Or Refractory Non-Hodgkin’s Lymphoma http://bit.ly/1q4tvPp

PNT2258 is a first-in-class DNAi consisting of a native, single-stranded, chemically unmodified DNA oligonucleotide delivered to a nuclear genomic target via a protective lipid nanoparticle, and the first to target the regulatory upstream region of the BCL2 gene. PNT2258 is well tolerated with an acceptable safety profile and shows significant single agent anti-tumor activity in pts with heavily treated relapsed NHL, particularly in pts with FL. Additional studies are planned.


Pronai Therapeutics reports positive results from PNT2258 Phase II study on lymphoma http://bit.ly/1B9gKGD

* Full text: A phase 1 study of the BCL2-targeted deoxyribonucleic acid inhibitor (DNAi) PNT2258 in patients with advanced solid tumors http://1.usa.gov/Z53YLF
 
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Testing ACP 196 (next gen BTK inhibitor) in Mantle Cell Lymphoma  http://1.usa.gov/1w6GhkC

Anticipated to have greater specificity for the BTK pathway and therefore less toxicity ... based on animal studies.

Canine study describes properties of ACP 196: vetcancertrials.org/
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Testing MLN9708 (Ixazomib, GATA-3 inhibitor) for Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas http://1.usa.gov/1iEFBYz

MLN9708 is an investigational, potent, reversible, and specific 20S proteasome inhibitor (next generation Velcade with better anticipated safety profile)

Goal is to determine the extent to which MLN9708 inhibits GATA-3 (Trans-acting T-cell-specific transcription factor) expression, which is associated with poor prognosis, and whether GATA-3 expression represents a novel predictive biomarker for MLN9708 sensitivity.


Background - early results: “MLN9708, a Novel, Investigational Proteasome Inhibitor, in Patients with Relapsed/Refractory Lymphoma: Results http://bit.ly/1pdqkBR 
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PI3K Delta Inhibitor TGR-1202, in Combination With Brentuximab Vedotin for Hodgkin's Lymphoma Patients” http://1.usa.gov/1lBvVC8

Rationale: ASH Paper: - PI3K-δ Inhibitor TGR-1202 With Brentuximab Vedotin Synergistically Induces G2/M Phase Arrest and Cell Death In Hodgkin Cell Lines http://bit.ly/1qppOEu
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ASCO Post: “Novel Agents Show Activity in relapsed Non-Hodgkin Lymphoma”
including CRs http://bit.ly/1dSn1gv
Promising reports in this article - impressive outcomes - particularly for single agents in relapse setting.
Agent

BOLD names are
FDA approved agents


 
B or T cell 
 
Target
of Drug
 
Approved
Indication
or note
 
Queries

Locate
Studies on
ClinicalTrials.gov

 

Counting
 Clicks
as of
3/7/13


4,651
Find
Clinical Reports
on agent

 or current count >

 

Monoclonal antibodies (Mab)
  See also Immune mediated

Monoclonal antibodies (MAbs) are similar to antibodies produced by the body in response to infection.  MAbs bind to specific receptor expressed on the tumor and some normal cells.
 

 

 
 
Agent name or class

Click to search for
 mechanism of action

 
 
Target
 
Find Trials
Count
Clinical Reports

 
 
MEDI-551 (humanized antibody) 
 

B cd19 - Find trials  61 Reports

>

 
cd-19-based antibodies
 

 

B cd19 - Find trials 21 Reports

>

 
 
Arzerra
® (Ofatumumab)
 
 

B cd20 - Find trials 203 Reports

>

 
Rituxan ® (Rituximab / Mabthera)
 
 

B cd20 - Find trials 84 Reports

>

 
GA-101 (Obinutuzumab)
 
 

B cd20 - Find trials 434 Reports

>

 
 
Ublituximab
 

B cd20 - Find trials 26 Reports

>

 
Veltuzumab / Immu-106 / Ha20
 

 

B cd20 - Find trials 15 Reports

 >

 
 
Epratuzumab
 

  

B cd22 - Find trials 91 Reports

 >

 
Lumiliximab

 

B cd23 - Find trials 45 Reports

 >

 
SGN-30

 

B / T cd30 - Find trials 58 Reports

 >

 
TRU-016

 

B cd37 - Find trials 107 Reports

 >

 
Zanolimumab

 

T cd4 - Find trials 65 Reports

 >

 
Campath ® (alemtuzumab)

 

B cd52 - Find trials 41 Reports

 >

  
MDX-1411
 

 

B / T cd70 - Find trials
 
58 Reports

>

 
Milatuzumab / hLL1
  
 

B cd74 - Find trials 53 Reports

 >

 
IMMU-114 (anti-HLA-DR)

  
 

  HLA-DR - Find trials 15 Reports

 >

  
Mogamulizumab
Mogo / KW-0761 / AMG-761

PAL
 

T CCR4 - Find trials 65 Reports 

>

Bispecific antibodies

Binding two receptors expressed on tumor cells and/or other immune cells
 

 


Agent name or class

  Target  

Find Trials

Count Reports

Counts

  
DT2219ARL

Bi
specific antibody with immunotoxin

  

B cd19 cd22 -  Find trials 131 Reports

>   >


 
Blinatumomab / MT103 / BiTe)
 
 

B cd3 cd19 -  Find trials 112 Reports

>

antibody-drug conjugates

Antibodies that deliver toxins to extracellular (CD) targets on tumor cells

Reports by class
 


Agent name or class

  Target  

Find Trials

 
Count

 
Reports

  
SGN-CD19A
anti-CD19 + toxin

 

B cd19 -  
Find trials
15 Reports

>

 
 
SAR3419
anti-CD19 + maytansinoi
 
  

B cd19 -
Find trials
114 Reports

>


Polatuzumab Vedotin

B cd22   Find trials New
Reports

>
 

 
DT2219ARL
anti-CD19 & 22 antibody + immunotoxin

 

B cd19 cd22 - Find trials 108 Reports

>

 
Inotuzumab Ozogamicin
anti-CD22 + calicheamicin

 

 

B cd22 - Find trials 214 Reports

>

 
DCDT2980S
anti-CD22, conjugated to MMAE

 

B cd22 - Find trials 22 Reports

>

 
LMB-2 immunotoxin
anti-CD25 antibody + immunotoxin
 

B cd25 - Find trials 30 Reports

>

 
Adcetris ® 
(SGN-35 / brentuximab vedotin)
anti-cd30 + antitubulin

 

B/T cd30 HL / ALCL Find trials 222 Reports

>


Radio-immunotherapy

Antibodies delivering radiation to tumor cells
 

 
Agent or class

  Target  

Find Trials

 
Count

6/23/14
 
Reports

 
Radioimmunotherapy
  
 

     

 
Find trials
 

3 Reports

>

 
Betalutin 
(Lu-tetraxetan-tetulomab)
 
 

B cd37 NHL Find trials 15 Reports

>

  
Bexxar ®
anti-CD20 + iodine 131
DISCONTINUED by GSK
 

B cd20 NHL Find trials 69 Reports

>

  
Zevalin ®
anti-CD20 + Yttrium 90

(Ibritumomab tiuxetan)
 
 

B cd20 NHL Find trials 113 Reports

>

   
epratuzumab tetraxetan
anti-CD22 with fractionated Yttrium 90 
 
 

B cd22 - Find trials 71 Reports

>

Immune-mediated

Immune mediated therapy assists in helping the immune system to attack the tumor.

See also antibody agents, and radioimmunotherapy
 

 
Agent or class

  Target  

Find Trials

Count Reports
Get Counts

 
 Anti-PD-1 antibody

   Pidilizumab (CT-011)

   BMS-936558 (
nivolumab)

    Lambrolizumab (Merck)
 
 
(Immune checkpoint blockade)

B PD-1 (P7) - Find trials 272

Reports

>   >   >   >

 
Ipilimumab

anti-CTL-A (MXD-010)

(Immune checkpoint blockade)

B CTL-A
t-reg
-

Find trials

15 Reports

>


 Immunocytokine therapy

Two immune components – antibodies and cytokines

- - - Find trials
>
 
6 Reports

 
 Revlimid ® / Lenalidomide / CC 5013

(Immune modulating / cereblon)
 

- unknown MDS / myeloma Find trials 95 Reports

>

Lenalidomide AND Rituxan

- unknown + cd20 New combination Find trials
 
4  
Reports

 >
 

 Pomalidomide  (Immune modulating)

- unknown NEW Find trials 5  
Reports

>
 

 
 T-cell therapy (adoptive immunotherapy)
 

B or T - - Find trials 14

>

 
cd19 CAR T-cell therapy

CAR - chimeric antigen receptor / adoptive immunotherapy  PAL

B cd19 148   Find trials>
184
 
Reports

 >  > | >

Vaccine (idiotype) therapy

B tumor antigen - Find trials 32 Reports

 >
 

Cytotoxic Agents

Damage the DNA of rapidly dividing cells, triggering apoptosis (programmed cell death)
 

 

 
Agent

  Target  

Find Trials

Count Reports / Count


 
Treanda ®

(Bendamustine)
 
 
 

B or T DNA NHL/CLL Find trials 78 Reports

>


 
Bendamustine
phase 3 trials
 

B or T DNA NHL/CLL Phase 3 trials 25 Reports

>

 
Folotyn ® (Pralatrexate)
 

- DNA T-cell Find trials 6 Reports

>

 
Pixantrone
 

Request:  Open Studies >
   

B DNA - Find trials 7

Reports

>


Targeted Agents
 

    


Epigenetic Agents

Agents that modify gene expression (by methylation or acetylation of histones and other elements) can reprogram how tumor cells behave: grow, die, or differentiate by activating or turning on genes.


DNA
methylation

can reactivate tumor suppressor genes by altering methylation

Hypermethylation-associated silencing of tumor suppressor genes has been shown to occur in lymphoid/hematopoietic malignancies, disrupting many cellular pathways.1-3 Unlike genetic alterations in cancer, hypermethylation changes are potentially reversible by pharmacologic inhibition of DNA methylation.4 The cytidine analogs 5-aza-2′-deoxycytidine and 5-azacytidine are capable of reactivating tumor suppressor genes that were silenced by hypermethylation.4

Agent

  Target  

Find Trials

Count  
Reports /Counts
 

 
Vidaza ®
 
(5-Azacytidine)
 
 

B DNA hypo-methylation  
 Find trials
 
20 Reports

>  >

HDAC inhibition

interferes with the function of histone deacetylase - modifying gene expression    About by PAL

 

 
Agent

  Target  

Find Trials

Count Reports / Counts

 
Abexinostat (PCI-24781)
 
 

  HDAC   Find trials 25 Reports

 >

 
Belinostat (PXD101)
 
 
T or B HDAC   Find trials 32 Reports

 >

 
Panobinostat (LBH589)
 
 
T or B HDAC   Find trials 54 Reports

  >

 
Romidepsin ® (Depsipeptide)
 
 
T or B HDAC Approved for T-cell lymphoma Find trials 21 Reports

 > 

 
Valproic acid
 
 
T or B HDAC AML / MDS Find trials 78 Reports

  >

 
Zolinza ® (Vorinostat)
 
 
T or B HDAC Approved for T-cell lymphoma Find trials 87 Reports

 >


targeting BCL-2
(apoptosis activation)

Binds to BCL-2 pathway involved in the blocking of apoptosis (programmed cell death)
 

 


Agent

- Target -

Find Trials

Count Reports / Counts

 
ABT-199 
 
 

B bcl-2
pathway
- 

Find trials

54  
Reports

 >

ASCO report
 


Obatoclax mesylate / GX15-070)
 
 
B bcl-2
pathway
-

-

Find trials 51  
Reports

>
 

mTOR

Binds mTOR pathway that promotes survival and cell growth
 

 

 
Agent

  Target -

Find Trials

Count Reports / Counts

CC-223

dual mTOR inhibitor (oral)
B mTOR - Find trials 21  
Reports

>
 


Everolimus / RAD001 (oral)
B mTOR -- Find trials 52  
Reports

>

Leukemia report
   


Temsirolimus / CCI-779 (IV)
B mTOR -- Find trials
 
38  
Reports   >
 

 
Kinase inhibitors

Inhibit pathways that are overactive in cancer cells
 

See also Agents that target disease pathways
 
     B-cell Receptor pathway
 
 
 
Target
 
      Reports | Counts

AVL-292

 
 
B BTK - Find trials 98
Reports

>
 


ACP-196
 

B BTK   Find trials   >
 
Idelalisib / GS-1101 / CAL101

 
 

B PI3k delta - Find trials 529  
 

Reports

 >
 


Ibrutinib
(PCI-32765) 

 
 

B BTK - Find trials 629  
 Reports

>
 


Ibrutinib
CLL studies
 

B - - Find trials 75 >

 
Ibrutinib
lymphoma studies
 

B -- - Find trials
 
New >

 
IPI-145
 
 

B or T  
(PI3K)-delta / PI3K-gamma
 
- Find trials 27
Reports

>
 


    Other kinase inhibitors
 
 
Target
-
Find Trials
Count
Reports / Counts

 
AEB071 (Sotrastaurin)
 
 

subtype
of DLBCL
 
 Protein Kinase C Inhibitor
 
- Find trials
 
8


Reports

>
 


Alisertib (MLN8237)
  
 
T Aurora Kinase A - Find trials 23  
Reports

>
 
Also
http://bit.ly/18sChgG
 


Other targeted agents
 

 
 
Lymphoma / CLL trials of new agents with search of literature for underlined agent
 
bullet
Selinexor (KPT-330) lymphoma trial query - ClinicalTrials.gov http://1.usa.gov/1xs0cJv
Selective Inhibitor of Nuclear Export (SINE) KPT-330
Safety study in Patients With Advanced Hematological Cancer
http://1.usa.gov/1pPJNuo

Background article in Haematologica. Jul 2013:
Selective inhibitors of nuclear export for the treatment of non-Hodgkin’s lymphomas
http://1.usa.gov/1lVKX7u
 
bullet
** SAR 245409 is a potent oral pan-inhibitor of PI3K

     List Results - ClinicalTrials.gov http://1.usa.gov/1hyV6Wi
bullet
copanilisib (BAY 80-6946), is an intravenously administered compound that has significant activity
against alpha and delta isoforms of PI3K; the delta isoform has a role in B-cell signaling, development

     List results -  ClinicalTrials.gov http://1.usa.gov/1glACLs
bullet
PNT2258 DNAi molecule targets the noncoding, nontranscribed regulatory region of the Bcl2 gene.

       List Results - ClinicalTrials.gov http://1.usa.gov/1nQQad1 
bullet
XmAb5574 / MOR00208 (optimized cd19 Mab)  Find trials

About study drug From morphosys.com: http://bit.ly/1kiAP8s
bullet
Ruxolitinib  (inhibitor of cytokine-signaling) - Find trials 

Related Citations for PubMed (Select 22869151) - PubMed - NCBI

Background on this drug for other indications: wikipedia.org
bullet
Pilot Study of Ruxolitinib in Relapsed or Refractory Hodgkin Lymphoma and Primary
Mediastinal Large B-cell Lymphoma - Full Text View - ClinicalTrials.gov http://1.usa.gov/19YXLEf 
 
bullet
AZD6738 First Time in Patient Multiple Ascending Dose Study - http://1.usa.gov/19TnU1m
bullet
A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma http://1.usa.gov/15MC83D
bullet
A Study of the Safety and Pharmacokinetics of SAR245408 Tablets in Patients With
Solid Tumors or Lymphoma -   http://1.usa.gov/1d6jTxS
bullet

PF-05082566 As A Single Agent And In Combination With Rituximab  http://1.usa.gov/1b6LCby

CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies http://bit.ly/1aXT0cB 

PF-05082566 is an anti-CD-137 agonist antibody that is designed to help the immune system
go after the lymphoma cells with Rituxan attached to them."
 

bullet

Acetylon Announces Preclinical Data of ACY-1215 for the Treatment of Lymphoma
Highlighted at 12th International Conference on Malignant Lymphoma (ICML) |
Business Wire
http://bit.ly/1hDNjBL 

HDACs regulate the activity of tumor-suppressor genes and oncogenes that play
crucial roles in tumorigenesis37 and therefore have been studied as therapeutic
targets in solid tumors and hematologic malignancies

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337713/

Rocilinostat (ACY-1215) is a selective HDAC6 inhibitor with IC50 of 5 nM. It is
>10-fold more selective for HDAC6 than HDAC1/2/3 (class I HDACs) with slight
activity against HDAC8, minimal activity against HDAC4/5/7/9/11, Sirtuin1, and
Sirtuin2.


Agent

  Target  

Find Trials

Count Reports

Crizotinib

  ALK   http://1.usa.gov/1khJYwL   http://1.usa.gov/1olUwxA
PD 0332991
  Cdk - Find trials
>
19 Reports

ISIS 481464 (AZD9150)

antisense oligonucleotide
inhibitor of STAT3

  STAT3   Find trial
>
NEW Report
YM155
B survivin kinase - Find trials
>
61 Reports
proteasome inhibitors

MLN970 / Bortezomib /
Velcade
® , Carfilzomib,
CEP 18770 
  proteasome inhibitors - Find trials
>
10 Reports
TL32711  
  inhibitors of apoptosis   Find trials
 >
8 Reports

 
Discontinued agents
 

 
 
Enzastaurin

 
B C-beta - Find trials 25 Reports

>

Navitoclax / ABT-263 >
 
Discontinued due to improvement in safety with ABT-199 above
 
B bcl-2
pathway
- http://bit.ly/5fcv13 99 Reports
             

 

 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
Patients Against Lymphoma, Copyright © 2004,  All Rights Reserved.