After eight, long, hard years of work with the ACTG and Division of AIDS (DAIDS), the Oncology Committee was finally pushed out during the AIDS Clinical Trials Group (ACTG)'s recent recompetition. They have been told that no new Kaposi's sarcoma (KS) or non-Hodgkin's lymphoma (NHL) protocols will be allowed to open and that they should finish all remaining studies as soon as possible.
Instead of being bitter and vowing never again to work within a clinical trials network, a vast majority of the oncological investigators have found a new home with the National Cancer Institute (NCI) and its new AIDS Malignancy Consortium (AMC). While most of them will continue to do work with their AIDS clinical trial units (two are principal investigators of their sites), these oncologists can work with each other solely on AIDS-related malignancy studies. The AMC will consist of 13 awardees from various sites around the country. The investigators and sites are as follows:
Michael Caligiuri (Roswell Park Cancer Center, Buffalo); Tony Cheung (Mt. Sinai); Margaret Fischl (U. of Miami); Carl Freter (Georgetown); Alvin Friedman-Kien (NYU); Bill Harrington (University of Miami); Lawry Kaplan (UCSF/SFGH); Susan Krown (MSKCC); Sandy Levine (USC); Ron Mitsuyasu (UCLA); Dave Scadden (Harvard); Clayton Smith (Duke); and Jamie von Roenn (Northwestern).
Some of the sites have multiple investigators with a variety of expertise, including Ron Mitsuyasu and Steve Miles; Susan Krown and Dave Straus; Sandy Levine and Parkash Gill; and Jamie Von Roenn with Rich Ambinder (Hopkins) and Lee Ratner (Washington University). Over two-thirds of them have been ACTG investigators who know all facets of HIV disease--not just malignancies. Susan Krown and Lawry Kaplan were elected co-chairs of the AMC. Jamie von Roenn will chair the KS Working Group and Dave Scadden will welcome change. In a good faith gesture, DAIDS sent Bill Duncan and the wonderful Pamela Clax to discuss future collaboration.
ACTG Group Chair, Chip Schooley, gave a presentation about the new ACTG's Advanced Technology Laboratories (ATLs). He wants to do the AMC's virology and immunology assays within the ACTG. If the NCI can help AMC come up with some money to do this lab work, it would be wise for them to use the ACTG's ATLs. Margaret Fischl and Ron Mitsuyasu will act as liaisons to the ACTG's HIV and Immunology Research Agenda Committees, respectively.
Stealing the show, however, was Jeannette Lee's presentation on behalf of the University of Alabama at Birmingham (UAB) which was awarded the RFA to be the operations and statistical center for the AMC. In these past two months, UAB's performance has been exemplary.
The meeting really got going during a free-wheeling discussion concerning money. Ellen Feigal was put in the hot-seat when Sandy Levine opened with her questions:
Levine: How do you think we are going to put 30 patients on a year with the amount of money that we have been given?
Feigal: It was a guesstimate. I didn't know it was going to be a problem.
Levine: It is a problem. I know how many patients an oncology nurse can take care of and it's not 30. These patients are very sick and need lots of care.
It was refreshing that the subject of too little money was being brought up. TAG has been one of the only public voices for the past 11 months insisting that two million dollars for this RFA is simply not enough! Maybe these investigators wanted to be chosen and had a foot in the door before they started complaining.
More money talk arose later when the group was instructed to discuss future research priorities and what protocols should be done. Dave Scadden, usually gentlemanly and reserved, spoke up:
Scadden: With the limited amount of funds, how should we prioritize? Is the horizon any broader?
Feigal: Choose the concept sheets that you think are the best and we will move forward. We will probably only be able to do two studies a year even though we planned on doing 4 to 6.
Scadden: With the death of the ACTG, who is going to do phase III standard-of-care studies?
Feigal: We can discuss the logistics issues and the resources later. I can't promise you millions of more dollars until we have put the first patient on. We can go back. We think they will listen. Dr. Wittes [second-in-command at the NCI] wants to see how many patients can go on and then he will see about more money.
Dave Scadden should be applauded for insisting that Phase III studies not be forgotten. The expertise exists within the AIDS Malignancy Consortium (AMC) to do Phase III studies, but funding does not. On-going negotiations and the strengthening of alliances with the NCI's Cooperative Oncology Groups (COGs) are essential for continuing all phases of AIDS malignancy clinical research.
The rest of the meeting focused on what scientifically important concept sheets could be quickly turned into protocols so that studies could be up and running in early 1996. From that discussion--and more recent ones on conference calls--the group has decided on six studies worthy of pursuing as formal protocols, which are in various stages of development. They are:
Oral 9-cis retinoic acid for Kaposi's sarcoma (KS)
SU-101, a VEGF (vascular endothelial growth factor) and BFGF (basic fibroblast growth factor) inhibitor for Kaposi's sarcoma
Interferon + a protease inhibitor (Merck's indinavir or Abbott's ritonavir) for KS
5-Azacytidine (5-AC) for EBV-positive refractory NHL
IL-12 for either up-front or refractory NHL
IL-2 for patients for NHL as a maintenance/prophylactic strategy after patients have achieved a partial response or complete response
These are all doable and have sound rationales for going into human study. There were many other interesting protocols that either had concepts which were too difficult or which had a schema for a drug which was not yet available. Once a study or two is done, then more challenging concepts can hopefully move forward if there is funding. We must wait and see.
This report was prepared by TAG's Michael Marco, who will serve as the community representative on the Steering Committee of the nascent AIDS Malignancy Consortium.