Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease.
OBJECTIVE
The purpose of this study was to evaluate the clinical activity and toxicity of recombinant human Interleukin (IL)-12 in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD).


METHODS
Forty-two previously treated patients (32 patients with NHL and 10 patients with HD) were enrolled on the study. Patients were treated with either intravenous (n = 11) or subcutaneous (n = 31) administration of IL-12. The patients had received a median of three prior treatment regimens, and 16 patients had undergone prior autologous stem cell transplantation.


RESULTS
All patients were assessable for toxicity, and 39 of 42 (93%) patients were assessable for response. Six of 29 (21%) patients with NHL had a partial or complete response, whereas none of the 10 patients with HD responded. Furthermore, 15 patients had stable disease that lasted for up to 54 months. Progression-free survival in patients with indolent NHL, aggressive NHL, and HD was 6, 2, and 2.5 months, respectively. Treatment was well tolerated, and the most common toxicity was flu-like symptoms. Reversible grade 3 hepatic toxicity was observed in three patients requiring dose reduction. IL-12 therapy increased the median number of peripheral blood CD8 T lymphocytes from 423/microl to 576/microl (P = 0.0019). Furthermore, IL-12 therapy decreased serum vascular endothelial growth factor and basic fibroblast growth factor concentrations in 37% of the patients.


CONCLUSIONS
The ability of recombinant human IL-12 therapy to increase the number of circulating CD8+ cells and induce clinical remissions in patients with relapsed NHL warrants further investigation of the drug.
Younes
Anas
A
Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ayounes@mdanderson.org
Pro
Barbara
B
Robertson
Michael J
MJ
Flinn
Ian W
IW
Romaguera
Jorge E
JE
Hagemeister
Fredrick
F
Dang
Nam H
NH
Fiumara
Paolo
P
Loyer
Evelyne M
EM
Cabanillas
Fernando F
FF
McLaughlin
Peter W
PW
Rodriguez
Maria Alma
MA
Samaniego
Felipe
F
D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D012008:Recurrence; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D011994:Recombinant Proteins; D018664:Interleukin-12