CLL DRUGS in DEVELOPMENT/APPROVED FOR CLINICAL USE

(please note, that for additional related articles on each drug, please click on the "related articles"link at the top right of the page after the individual Medline (Entrez) abstract is chosen)

Preclinical Development/Exploratory Approaches

• AN-9(butyric acid derivative) Ц induces apoptosis in HL-60 cells in tissue culture.

• CpG-oligonucleotides

• Doxorubicin Ц in combination with AN9 in vitro in lymphocytes from CLL patients reduce bcl-2 and enhanced bax expression.

• vinorelobine

• nitric acid donors (e.g.,PAPA-NO)
    • IL-4 and Interferon gamma

• CD80 and IL-15

• PKC412 Ц protein kinase C inhibitor

• LMB12 Ц anti-CD25 immunotoxin

• CLL is a heterogeneous disease Ц role of surface immunoglobulin as drug targets

• vaccine-based immunotherapy - dendritic cells

• KRN 5500 (capase-dependent apoptosis activator)

• IL-8 Inhibitors

• Resveratrol and other Polyphenols

• Triterpenoids

• Retinoid (CD437/AHPN)

• Phosphodiesterase type 5 Inhibitors (Sildenafil-Viagra)

• PRO64553 (anti-CD40) monoclonol antibody

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Clinical Development - Early (Phase I)

• BL22 (immunotoxin)
    • abstract 1
    • abstract 2

• 4G7xH22

• Hu1D10

Clinical Development - Intermediate (Phase II)

• Gemcitabine

• Genasense

• SDX-101

• Bryostatin

• PS-341 (proteasome inhibitor)
    • clinical trial protocal
    • preclinical abstract
    • proteasome inhibitor sponsor webpage

• Combined Retuximab/Campath-I therapy

• Thalomide®; (thalidomide)
    • study summary

• A10 and AS2-1

Clinical Development - Late (Phase III)

• Campath® (Multicenter Open-label Trial)

• Genasense (with fludarabine and cyclophosphamide)
    • general overview
    • clinical program overview

Presently no new drugs are in Phase III as first line therapy alone, except for the Campath® open-label study. There are a number of studies being conducted for drug-drug combinations for improving the response of marketed first line drugs as well as treating CLL-related complications (See NCI Clinical Trials link and Adjunct Therapy section below.). There are also clinical trials ongoing related to improving patient survival after bone marrow/stem cell transplant as well as salvage therapy.

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Clinical Development - Post Market (Phase IV)

• Leukeran® (Chlorambucil)
    • versus fludarabine as first line therapy
    • clinical trial protocol

• Fludara® (fludarabine)
    • comparison with chlorambucil

• Nipent® (pentostatin)
    • in combination therapy
    • poor tolerance

• Cladrabine® (2-chlorodeoxyadenosine)

Adjunct Therapy (Second Line) Цdrug-drug combinations

• Overview

• Rituxan® (rituximab)

      • enhanced activity

      • future directions

      • Rituxan web page

• Campath®(Campath-1H, alemtuzumab)

      • Campath® web page

• pregnisone

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• Sandimune® (Neoral®) (cyclosporine A)
    • modest antileukemic effect in CLL patients Ц RX for cytopenia
    • replacing high-dose cytotoxic therapy with graft-versus-tumor effects

• PSC-833 (cyclosporine A analog)
    • blockade of multi-drug resistance

• cyclophosamide
    • with low dose fludarabine
    • comparison of fludarabine with fludarabine plus cyclophosamide
    • with cladrabine

• Arsenic Trioxide
    • Effect on leukemia cell lines in vitro
    • Brief clinical trial

• thrombopoietin

• erthropeoetin

• G-CSF

• IL-II

• CHOP

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Complementary Medicine

• exercise
    • antileukemic effect of endurance training

• nutrition
    • NCI eating tips for cancer patients

• meditation
    • mind-body medicine Ц a review of the literature
    • A primer for alternative and complementary medicine
    • Integrating mind-body practices with traditional therapy

• genetics and epidemiology

• NCI Division of Genetics and Epidemiology

Drugs Classified by Mechanism of Action

• Inhibitors of DNA synthesis - Purine Nucleosides
    • 2-fluoro-ara-AMP(fludarabine)
    • 2-deoxycoformycin(pentostatin)
    • 2-chlorodeoxyadenosine (cladribine)
    • gencitabine

• Monoclonol Antibodies
• Overview
    • engineered antibodies
    • monoclonal antibodies and future research direction
    • Rituximab (Retuxan®)(anti-CD20)
    • Campath® (alemtuzumab)(anti-CD52)
    • Mylotarg® (anti-CD33)
    • 4G7xH22
    • Tostitumomab-131I (Bexxar®;)
    • Ibritumomab tiuxatan (Zevalin®)(I131-labled Retuxan®)
    • Hu1D10 (anti-class II HLA)
    • PRO64553 (anti-CD40)

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• Immunotoxin
    • BL22
    • LMB12

• Antisense
    • Genasense®

• Proteasome inhibitor
    • PS341

• Protein kinase C Activator
    • Bryostatin

• Protein kinase C inhibitor
    • PKC412

• Anti-angeogenesis
    • thalidomide

• Anti-neoplastin
    • A10
    • AS2-1

• Alkylating Agent of the nitrogen mustard type
    • chlorambucil

• Inorganic (miscellaneous)
    • arsenic trioxide

• Vaccines

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Pharmaceutical/Biotech Companies with drug discovery/development programs
for CLL or possible CLL-related indications

    • Berlex Pharmaceutical Corp
    • BioChem Pharmaceutical Corp
    • Celgene
    • Corixa Corporation
    • Directory of Pharmaceutical companies
    • Drug Discovery Online
    • Genentech, Inc
    • Genta
    • Glaxo SmithKline Beacham
        • clinical trial
    • IDEC Pharmaceutical Corp
    • ILEX Oncology
    • Ligand Pharmaceutical Corp
    • Millennium Pharmaceutical Corp
    • NeXstar Pharmaceuticals
    • Polaex
    • Protein Design Labs
    • Salmedix
    • SuperGen
    • U.S. Bioscience, Inc.
    • Wyeth

    • Drug companies with patient assistant programs for medication