A Pilot Study of the Combination of Retinoic Acid and Interferon-Alpha2a for the Treatment of Lymphoproliferative Disorders in Children With Immunodeficiency Syndromes
Patients with congenital or acquired immunodeficiencies are at an increased risk to develop
polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative
disorder that can follow a clinically aggressive course and may represent a pre-malignant
lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell
or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially
understood. The Epstein-Barr virus (EBV) is thought to play an important role but the human
herpes virus type 6 (HHV-6) has been implicated as well. An imbalance in the expression of
several cytokines is observed and it is currently not clear whether this sustains the
aberrant proliferation or is a result thereof. In the case of pre-malignant conditions it
is often difficult to know when and whether a therapeutic intervention is necessary and a
careful consideration of potential treatment-associated morbidity is indicated. Therapies
have ranged from influencing the possible infectious etiology (by treating with acyclovir),
decreasing the amount of immunosuppression (in transplant patients), to the use of
immunomodulatory agents, including interferons and interleukins. Recent data have indicated
that the use of differentiating agents, such as the retinoids, might offer yet another
treatment option. In the current study we will try to get a better understanding of the
pathogenesis and natural course of lymphoproliferative disorders in immunodeficient
children. The study will mainly be open to children infected with the human
immunodeficiency virus but patients who develop a lymphoproliferative disorder
post-transplant or as part of another immunodeficiency state may also be enrolled. The
study will have two parts: an initial observation period to obtain information on the
natural course of these disorders, and then a six month treatment period with the
combination of a differentiating agent (13-cis-retinoic acid was used until
all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent
(interferon-alpha2a, IFN-alpha2a).
Interventional
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
United States: Federal Government
950144
NCT00001438
June 1995
December 2000
Name | Location |
---|---|
National Cancer Institute (NCI) | Bethesda, Maryland 20892 |