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.
Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. ayounes@mdanderson.org
Anas
A
Younes
Barbara
B
Pro
Michael J
MJ
Robertson
Ian W
IW
Flinn
Jorge E
JE
Romaguera
Fredrick
F
Hagemeister
Nam H
NH
Dang
Paolo
P
Fiumara
Evelyne M
EM
Loyer
Fernando F
FF
Cabanillas
Peter W
PW
McLaughlin
Maria Alma
MA
Rodriguez
Felipe
F
Samaniego
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