AIDS TREATMENT NEWS #140, December 6, 1991
Michelle Roland

The specific agent being studied is one of a group of compounds called "immunotoxins." Immunotoxin molecules consist of two parts: a specific antibody which targets the molecule to a certain kind of cell, and a toxin which kills the cell. The drug being studied in San Francisco is called "ricin-A chain conjugated anti-CD22." It was designed to bind to the CD-22 marker found on many of the B-cell lymphomas seen in people with AIDS, allowing the toxin (ricin-A chain) to enter and kill the cells.

This immunotoxin approach has been studied in HIV-negative people with lymphomas which have been unsuccessfully treated with the standard medical approaches of chemotherapy and radiation. It appears to be a promising concept which will eventually be used in combination with other immunotoxins and chemotherapy drugs. It is extremely important that new and creative approaches are pursued in developing treatments for lymphoma, as those which are currently available have both limited effectiveness and substantial side effects.

The study at San Francisco General Hospital will include approximately 25 patients who have not responded to, or have relapsed after, standard therapy. Biopsies will be required to make sure that enough of the lymphoma cells have CD22 receptors on them to make it likely that the immunotoxin will be effective.

The side effects of this therapy, as seen in studies in HIV- negative volunteers, appear to be limited. The most common side effects seen so far include muscle aches, reversible weight gain, and accumulation of fluid in the tissues (edema). When edema occurs in the lungs it can be very serious; in past studies people have died from pulmonary edema. Therefore, people with lymphomas involving the lungs will not be allowed to participate in this study.

Volunteers will be excluded if, in addition to lymphoma, they also have certain active opportunistic infections which require treatment, or are using the growth factors G-CSF or GM- CSF. If an opportunistic infection develops while on the study, the study medication will be stopped until the infection is treated. Maintenance or preventive treatment for MAC, cryptococcal meningitis, and tuberculosis are allowed.

The study has two components. First, a dose escalation phase will find the maximum tolerated amount of the drug. This will be done by starting with a very small dose in three people, and increasing the dose in subsequent groups of three. The maximum tolerated dose will be used in the next phase, which will include about thirteen additional people, to evaluate the effectiveness of the treatment. The drug will be given by IV infusion four times over a period of eight days. The study requires eight to nine days of hospitalization in the clinical research center at San Francisco General Hospital.

The cost of hospitalization, the drug, and all tests directly associated with the study will be covered. However, costs of exams and tests associated with the standard care of a person with AIDS-associated lymphoma will be billed to the participant's insurance company, MediCal, or other third party payer. According to Lawrence Kaplan, M. D., the principal investigator of this study, billing for the costs of standard care of a person with lymphoma within the context of a clinical trial has not presented a problem at San Francisco General Hospital in the past. For more information about this study, Dr. Kaplan can be reached at 415/476-4082, extension 84190.

Another Lymphoma Study: Sites Throughout U. S.

People with lymphoma should also be aware of another large, multi-center study called ACTG 142, which is testing a more conventional treatment approach. ACTG 142 is comparing high- dose versus low-dose chemotherapy, in combination with the growth factor GM-CSF, to determine if high-dose chemotherapy will be more effective than a more conservative low-dose regimen. This study is enrolling patients at 22 sites around the country.

ACTG 142 is typical of most of the studies available today which involve the use of varying doses and combinations of chemotherapy, radiation, and growth factors. Often they do not offer drugs which are not available through a clinic or doctor's office; therefore, private physicians may not refer their patients to these studies. While a major incentive for participating in clinical research is often the opportunity to try experimental therapies which are otherwise unavailable, it is also important to systematically collect information about less exciting, but often important, treatment questions.

For example, all of the drugs in ACTG 142 (or very similar ones) are available through clinics and private physicians. But the only way to reliably learn how well different regimens work is to collect data in a consistent and coordinated manner through a clinical trial.

ACTG 142 is enrolling volunteers very slowly. It is mentioned it here because there are two very important components to AIDS lymphoma-related research. The more exciting, and potentially much more useful, is to develop completely new approaches to lymphoma treatment. The immunotoxin therapies are one such novel approach which should be pursued actively and quickly. Treatment advocates should be aware of the development of these compounds so that, if they are shown to be safe and somewhat effective as single agents, they can be pushed as quickly as possible into combination trials.

The second (less exciting) research direction seeks to help people with AIDS-related lymphomas and their physicians define the best way to use the drugs which are available to us today. This will happen only if doctors and patients participate in trials like ACTG 142, and if these trials are designed to be attractive to potential participants. For more information about this and other AIDS-lymphoma trials, excluding the immunotoxin study described in this article, call 800/TRIALS-A.

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