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Patients Against Lymphoma

 

Locate Trials by Type of Agent 

This resource is an aid in the discussion of trials -- tools for patients, caregivers, and oncologists -
requiring no registration steps or the disclosure of personal information.

 Of special interest | What's New        Last update:  06/17/2015

By Class: 
   - Monoclonal antibody
   - Bispecific antibody
   - Antibody-drug conjugates 
   - Radioimmunotherapy
   - Immune mediated | PD-1 antibody
   - Cytotoxic

Targeted  
   - Epigenetic agents
   - Apoptosis - activating programmed cell death  
   - Kinase inhibitors (e.g., ibrutinib) | mTOR | Other
   - Tumor suppressor gene

Agents that Target Disease Pathways  PDF 

Dose - the importance of getting it right

 
Study Results for Lymphoma and CLL trials -
shows start and end dates, number enrolled
 


Agents with recent encouraging clinical reports

bullet
ABT-199  (Venetoclax) (activating apoptosis) Find trials
bullet
Adcetris ®  SGN-35 / brentuximab vedotin  (antibody-drug conjugate: anti-cd30 + antitubulin)  Find trials
bullet
ACP-196 (targeting btk pathway)  Find trials
bullet
Belinostat PXD101 (epigenetic - recent approval) Find trials
bullet
Cd19 CAR T-cell therapy (adoptive immunotherapy)  Find trials 
bullet
GA-101 (Obinutuzumab), next generation cd20 antibody  Find trials
bullet
Lenalidomide (immune modulation and direct activity)  Find trials
bullet
Ibrutinib (all - recent approval for CLL; inhibiting btk - on b-cell receptor pathway) Find trials
bullet
Ibrutinib for Lymphoma only  Find Trials
bullet
Idelalisib GS-1101 formerly CAL101 (inhibiting b-cell receptor pathway)  Find trials
bullet
PD1/L antibodies (activates immune system - immune checkpoint blockade)  Find trials  (updated)
bullet
Vidaza ®  5-Azacytidine (epigenetic - activating or shutting off genes) Find trials 


What's New

Daratumumab (Mab) | Mocetinostat  (HDAC)| ONC201 | XmAb5574 / MOR00208 (cd19 Mab) |  
bullet
CLL - Weill Cornell 2015:
FDA Grants Breakthrough Therapy Designation to Venetoclax (ABT-199)
for Patients with Relapsed/Refractory CLL with 17P Deletion http://bit.ly/1cmRGoX
bullet
Study drug of interest:
Testing Procaspase Activating Compound-1 (PAC-1) in Advanced Malignancies - lymphoma -- ClinicalTrials.gov http://1.usa.gov/1zXsWvV

* Background: Cell Death Dis. 2013 Dec; 4(12): e968.
Procaspase-activating compound-1 (PAC-1) a direct caspase-activating compound” http://1.usa.gov/1zp1pTi   
bullet
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)
 
bullet
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.
 
bullet
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

* 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
 
bullet
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/
bullet
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 
bullet
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
bullet
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

>

XmAb5574 / MOR00208
  

  cd19   Find trials New Reports

>
 

 
 
Arzerra
® (Ofatumumab)
 
 

B cd20 - Find trials 203 Reports

>

Daratumumab

  cd38   Find trials New 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

 >

 
Daratumumab
 

  cd39   Find Trials
 
New  

 
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 cd79b   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 ®
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)

 
   Lambrolizumab (nivolumab)

    Pembrolizumab 

    MPDL3280A
 
 
(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

 >

Mocetinostat

  HDAC   Find trials New 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

 >


Apoptosis activation

Target pathways involved in the blocking of apoptosis (programmed cell death)


Agent

- Target -

Find Trials

Count Reports / Counts

 
ABT-199  (Venetoclax)
 
 

B bcl-2
pathway
- 

Find trials

54  
Reports

 >

ASCO report
 


PNT2258

  bcl-2 pathway nanoparticle delivery   Find trials NEW >


Procaspase Activating Compound-1 (PAC-1)

  activating caspase   Find trials NEW >

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
B mTOR -- Find trials 52  
Reports

>

Leukemia report
   


Temsirolimus / CCI-779 
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 NEW >
 
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 (Duvelisib)
 
 

B or T  
(PI3K)-delta / PI3K-gamma
 
- Find trials 47

query updated

Reports

>  >
 


Alisertib (MLN8237)
  
 
T Aurora Kinase A - List results - ClinicalTrials.gov 23  
Reports

>
 
Also
http://bit.ly/18sChgG
 


Activating tumor suppressor gene
 

 


APTO-253 (LOR-253)

      List results - ClinicalTrials.gov New  


Selinexor (KPT-330)
 

Nuclear Export     List results - ClinicalTrials.gov NEW >


Other targeted agents

Lymphoma / CLL trials of new agents with search of literature for underlined agent
 
bullet
ACY-1215 (Ricolinostat)

HDAC6 inhibitor

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 

* List Results -  ClinicalTrials.gov
 
bullet
AEB071 (Sotrastaurin)

PKC inhibitor   | AACR report

* List results - ClinicalTrials.gov 
>
 
bullet
AZD6738

orally bio-available inhibitor of ataxia telangiectasia and rad3 related (ATR), a key serine/threonine protein kinase involved in DNA damage response signaling caused by DNA replication associated stress.  

* First Time in Patient Multiple Ascending Dose Study http://1.usa.gov/19TnU1m
 
bullet
Copanilisib (BAY 80-6946)

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
 
bullet
CPI-0610

A small molecule inhibitor of the Bromodomain and Extra-Terminal (BET) family of proteins

* A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma http://1.usa.gov/15MC83D
 
bullet
Crizotinib

anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011,

* List results -
ClinicalTrials.gov

 
bullet
Entospletinib  (GS-9973)

Oral, selective inhibitor of spleen tyrosine kinase (Syk)

Dr Sharman's Blog 2015: Syk not Sick http://bit.ly/1z5fvVz 


Dr Sharman discusses yet another pathway targeting drug: "Entospletinib looks to have pretty good efficacy in CLL. It is a twice daily pill. You really cannot compare across studies, but some of the early numbers look a lot like idelalisib. Lots of work left to be done and the trial is still recruiting patients with CLL (trial link here). Talk to your own doctor or seek an opinion at one of the centers offering the trial."

* List results - ClinicalTrials.gov 
 
bullet
ISIS 481464 (AZD9150)

antisense oligonucleotide inhibitor of STAT3

* List results - ClinicalTrials.gov  
>
 
bullet
ONC201

Exerts p53-Independent Cytotoxicity Through TRAIL and DR5 Induction In Mantle Cell Lymphomas http://bit.ly/1HtPIya

* Dose-finding safety Study of Oral ONC201 in relapsed Non-Hodgkin's Lymphoma - ClinicalTrials.gov
 
bullet
PD 0332991 (palbociclib)

cyclin-dependent kinase (CDK) 4/6–specific inhibitor  | Reports

* List results ClinicalTrials.gov  >
 
bullet
PF-05082566  

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

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

* Study of PF-05082566 as single Agent And In Combination With Rituximab  http://1.usa.gov/1b6LCby
 
bullet
PNT2258

DNAi molecule targets the non-coding, non-transcribed regulatory region of the Bcl2 gene.


*   List Results - ClinicalTrials.gov 
 
bullet
proteasome inhibitors

MLN970 / Bortezomib /  Velcade
® , Carfilzomib,  CEP 18770 

* List trials - ClinicalTrials.gov
 
bullet
Ruxolitinib  

Janus Kinases (JAK) inhibitor

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

Background on this drug for other indications: wikipedia.org


* Pilot Study of Ruxolitinib in Relapsed or Refractory Hodgkin Lymphoma and Primary
Mediastinal Large B-cell Lymphoma - Full Text View - ClinicalTrials.gov 


* List results - ClinicalTrials.gov 
 
bullet
SAR245409 (Voxtalisib)

An oral pan-inhibitor of PI3K and mTOR

 * List Results - ClinicalTrials.gov
 
bullet
SAR245408

Pan- PI3K inhibitor

* A Study of the Safety and Pharmacokinetics in Patients With Solid Tumors or Lymphoma - http://1.usa.gov/1d6jTxS
 
bullet

YM155

Survivin kinase inhibitor  * Reports

* List results
ClinicalTrials.gov  >  61 looks
 

bullet

bullet

 
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
TL32711 (birinapant)

Reports
* Search results ClinicalTrials.gov  >
           

 

 
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For all medical concerns,  you should always consult your doctor. 
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