Download Table S3. Clinical trials regarding immunotoxins

Table S3. Clinical trials regarding immunotoxins
Conjugate
Clinical trial
identifier
NCT00967577
NCT00077922
NCT00080535
NCT00389506
NCT00321555
NCT00295958
NCT00085150
NCT00002765
Drug
Target
Stage
Cancer
Effects
Pseudomonas
Aeruginosa
exotoxin (PE38)
Tac (CD25)
Pilot study,
I, II
ATL,
CLL,
CTCL,
HL,
HCL,
Metastatic Melanoma,
Pediatric Leukemias
Lymphomas
1, 2
BL22
NCT00126646
NCT00021983
NCT00074048
NCT00924040
Pseudomonas
Aeruginosa
exotoxin (PE38)
CD22
I, II
CLL,
CD22+ Lymphomas
3, 4
SS1(dsFv)PE38
NCT00066651
NCT00006981
NCT01041118
NCT01051934
NCT01362790
Pseudomonas
Aeruginosa
exotoxin (PE38)
Mesothelin
I
5, 6
LMB-9
NCT00019435
NCT00005858
Pseudomonas
Aeruginosa
exotoxin (PE38)
Lewis Y
I
LMB-1
NCT00001805
Pseudomonas
Aeruginosa
exotoxin (PE38)
Lewis Y
I
MR1-1KDEL
NCT01009866
EGFRvIII
I
CAT-8015
NCT01030536
NCT01086644
CD22
I, II
NHL,
CLL
3
RFT5-dgA
NCT00667017
NCT01378871
NCT00586547
NCT00586274
Pseudomonas
Aeruginosa
exotoxin (PE38)
Pseudomonas
Aeruginosa
exotoxin (PE38)
deglycosylated
ricin toxin Achain (dgA)
Cervical Cancer,
Fallopian Tube Cancer,
Head and Neck Cancer,
Lung Cancer,
Malignant Mesothelioma,
Ovarian Cancer,
Pancreatic Cancer,
Primary Peritoneal Cavity
Cancer
Bladder Cancer
Breast Cancer
Colorectal Cancer
Esophageal Cancer
Gastric Cancer
Lung Cancer
Pancreatic Cancer
Breast Neoplasms
Colonic Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms
Supratentorial
Malignant
Brain Tumor
CD25
I, II
Relapsed/Refractory CTCL,
Relapsed/Refractory
ATL/Lymphoma
9-11
RFB4SMPT-dgA
NCT00001271
NCT00007956
deglycosylated
ricin toxin Achain (dgA)
CD22
I
Refractory CD22 Positive BCell Lymphoma
20
Denileukin
diftitox
NCT00224354
NCT00357448
NCT00945269
NCT00425672
NCT00117845
NCT00003615
Diphteria toxin
(DT389)
CD25
I, II
CLL,
Advanced Stage Ovarian
Cancer,
Metastatic Melanoma,
Advanced Refractory Breast
Cancer,
ATL,
Stage II, III, and IV Follicular
Low-Grade NHL
9-13
LMB-2
and
7
8
Not
yet
available
HuM195/rGel
NCT00038051
recombinant
plant
toxin
gelonin (rGel)
CD33
I
AML,
CMML,
Myeloproliferative
Disorders,
Anemia, Refractory, With
Excess of Blasts
Leukemia,
Lymphoma
21
DT2219ARL
NCT00889408
Diphteria toxin
(DT389)
I
UCHT1
NCT00611208
ABR217620
NCT00420888
NCT00132379
NCT00056537
Diphtheria
toxin (catalytic
and
translocation
domains)
staphylococcal
enterotoxin E
CD19, CD22
(bispecific
antibody)
CD3
I, II
T-Cell Lymphomas,
T-Cell Leukemias,
Sezary Syndrome,
Mycosis Fungoides
14
5T4
I, II, III
Advanced Renal Clear Cell
Carcinoma,
Advanced Non-Small Cell
Lung Cancer,
Pancreatic Cancer
15,16
Denileukin
diftitox
NCT00224354
NCT00357448
NCT00945269
NCT00425672
NCT00117845
NCT00003615
Diphteria toxin
(DT389)
CD25
I, II
9-13
NCT00889408
Diphteria toxin
(DT389)
I
UCHT1
NCT00611208
I, II
T-Cell Lymphomas,
T-Cell Leukemias,
Sezary Syndrome,
Mycosis Fungoides
14
ABR217620
NCT00420888
NCT00132379
NCT00056537
Diphtheria
toxin (catalytic
and
translocation
domains)
staphylococcal
enterotoxin E
CD19, CD22
(bispecific
antibody)
CD3
CLL,
Advanced Stage Ovarian
Cancer,
Metastatic Melanoma,
Advanced Refractory Breast
Cancer,
ATL,
Stage II, III, and IV Follicular
Low-Grade NHL
Leukemia,
Lymphoma
DT2219ARL
5T4
I, II, III
Advanced Renal Clear Cell
Carcinoma,
Advanced Non-Small Cell
Lung Cancer,
Pancreatic Cancer
15,16
Not
yet
available
Not
yet
available
AML = Acute Myeloid Leukaemia; ATL = Adult T-Cell Leukaemia; CMML = Chronic
Myelomonocytic Leukaemia; CLL = Chronic Lymphocytic Leukaemia; CTCL = Cutaneous T-Cell
Lymphoma; HCL = Hairy Cell Leukaemia; HL = Hodgkin’s Lymphoma; NHL = Non-Hodgkin’s
Lymphoma
References
1.
2.
3.
4.
Kreitman RJ, Fitzgerald DJ, Pastan I. Approach to the patient after relapse of hairy cell leukemia.
Leuk Lymphoma. Oct 2009;50 Suppl 1:32-37.
Kreitman RJ, Wilson WH, White JD, et al. Phase I trial of recombinant immunotoxin anti-Tac(Fv)PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol. Apr 2000;18(8):1622-1636.
Kreitman RJ, Arons E, Stetler-Stevenson M, Fitzgerald DJ, Wilson WH, Pastan I. Recombinant
immunotoxins and other therapies for relapsed/refractory hairy cell leukemia. Leuk Lymphoma. Jun
2011;52 Suppl 2:82-86.
Kreitman RJ, Squires DR, Stetler-Stevenson M, et al. Phase I trial of recombinant immunotoxin
RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. J Clin Oncol. Sep 20
2005;23(27):6719-6729.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Kreitman RJ, Hassan R, Fitzgerald DJ, Pastan I. Phase I trial of continuous infusion anti-mesothelin
recombinant immunotoxin SS1P. Clin Cancer Res. Aug 15 2009;15(16):5274-5279.
Hassan R, Bullock S, Premkumar A, et al. Phase I study of SS1P, a recombinant anti-mesothelin
immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma,
ovarian, and pancreatic cancers. Clin Cancer Res. Sep 1 2007;13(17):5144-5149.
Hausner PF, Karp JE, Edelma NL, et al. Phase I study of LMB-9 (B3(dsFv)PE38), a recombinant
disulfide stabilized anti-Lewis Y immunotoxin ad- ministered by continuous infusion. Proc. Am.
Soc. Clin. Oncol. 2003;122(abstract 736).
Hassan R, Williams-Gould J, Watson T, Pai-Scherf L, Pastan I. Pretreatment with rituximab does
not inhibit the human immune response against the immunogenic protein LMB-1. Clin Cancer Res.
Jan 1 2004;10(1 Pt 1):16-18.
Foss F, Demierre MF, DiVenuti G. A phase-1 trial of bexarotene and denileukin diftitox in patients
with relapsed or refractory cutaneous T-cell lymphoma. Blood. Jul 15 2005;106(2):454-457.
Kuzel TM, Li S, Eklund J, et al. Phase II study of denileukin diftitox for previously treated indolent
non-Hodgkin lymphoma: final results of E1497. Leuk Lymphoma. Dec 2007;48(12):2397-2402.
Gerena-Lewis M, Crawford J, Bonomi P, et al. A Phase II trial of Denileukin Diftitox in patients
with previously treated advanced non-small cell lung cancer. Am J Clin Oncol. Jun 2009;32(3):269273.
Prince HM, Duvic M, Martin A, et al. Phase III placebo-controlled trial of denileukin diftitox for
patients with cutaneous T-cell lymphoma. J Clin Oncol. Apr 10 2010;28(11):1870-1877.
Natarajan N, Telang S, Miller D, Chesney J. Novel immunotherapeutic agents and small molecule
antagonists of signalling kinases for the treatment of metastatic melanoma. Drugs. Jul 9
2011;71(10):1233-1250.
Woo JH, Lee YJ, Neville DM, Frankel AE. Pharmacology of anti-CD3 diphtheria immunotoxin in
CD3 positive T-cell lymphoma trials. Methods Mol Biol. 2010;651:157-175.
Borghaei H, Alpaugh K, Hedlund G, et al. Phase I dose escalation, pharmacokinetic and
pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and
with docetaxel in patients with advanced non-small-cell lung cancer. J Clin Oncol. Sep 1
2009;27(25):4116-4123.
Robinson MK, Alpaugh RK, Borghaei H. Naptumomab estafenatox: a new immunoconjugate.
Expert Opin Biol Ther. Feb 2010;10(2):273-279.
Castelletti D, Fracasso G, Righetti S, et al. A dominant linear B-cell epitope of ricin A-chain is the
target of a neutralizing antibody response in Hodgkin's lymphoma patients treated with an anti-CD25
immunotoxin. Clin Exp Immunol. May 2004;136(2):365-372.
Schnell R, Borchmann P, Staak JO, et al. Clinical evaluation of ricin A-chain immunotoxins in
patients with Hodgkin's lymphoma. Ann Oncol. May 2003;14(5):729-736.
Schnell R, Vitetta E, Schindler J, et al. Treatment of refractory Hodgkin's lymphoma patients with an
anti-CD25 ricin A-chain immunotoxin. Leukemia. Jan 2000;14(1):129-135.
Sausville EA, Headlee D, Stetler-Stevenson M, et al. Continuous infusion of the anti-CD22
immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study. Blood. Jun
15 1995;85(12):3457-3465.
TargaTherapeutics.
Human
Clinical
Trials
Results
with
HuM195/rGel.
http://www.targatherapeutics.com/payloads.html.
Table S3: Details of the clinical trials involving immunotoxins (data gathered from US
clinicaltrials.gov, Clinical Trials register EU and available bibliography in sponsor an PubMed
websites).