H U M A N G E N E T H E R A P Y 1:441^142 (1990) Mary A n n Liebert, Inc., Publishers
TNF/TIL H u m a n Gene
Therapy
Clinical P r o t o c o l M E M O T O T H E R A C , J U L Y 6, 1990 July 6, 1990 Dr. Nelson Wivel Director of the Office of Recombinant D N A Activities Building 31, R o o m 4B11 Bethesda, Maryland 20892 Dear Dr. Wivel: I am submitting the attached protocol entitled, "Gene therapy of patients with advanced cancer using tumor infiltrating lymphocytes transduced with the gene coding for tumor necrosis factor" for consideration by the H u m a n Gene Therapy Subcommittee ofthe Recombinant D N A Advisory Committee at its meeting on July 30 and for consideration by the Recombinant D N A Advisory Committee at its meeting on July 31. This protocol has n o w received conditional approval by the Clinical Research Committees ofthe National ^ancer Institute (NCI-CRC), the National Heart, Lung and Blood Institute (NHLBI-CRC) and the Institutional Biosafety Committee of the National Institutes of Health (NIH-IBC). This protocol was considered by the Clinical Research Committee, N C I on M a y 14, 1990, and received conditional approval with the stipulations listed in the attached document from that committee. Each of these stipulations have n o w been met and have been incorporated into the protocol enclosed with this letter. Additional information was required by the Institutional Biosafety Committee, N I H and the Clinical Research Committee, N H L B I and to meet these requests an addendum to this protocol dated M a y 24, 1990, was prepared. This addendum presented additional background information but did not involve changes in the clinical protocol. The protocol was re-presented along with this additional information at a meeting of the Clinical Research Committee, N H L B I on June 5 and to the Institutional Biosafety Committee, N I H on June 6. Both of these groups then conditionally approved the protocol and the documents indicating this are enclosed with this letter. The enclosed documents therefore include: 1. The clinical protocol modified as requested by the Clinical Research Committee, NCI. 2. The addendum dated M a y 4 [Ed: M a y 24], 1990 containing the additional information required by the Institutional Biosafety Committee, N I H and the Clinical Research Committee, N H L B I . 3. Points to consider document. 4. Memoranda from the N C I - C R C , N H L B I - C R C , N I H - C R C . The conditional approval received from the NHLBI-CRC and from the NIH-IBC requested additional information from studies to be performed in immunosuppressed monkeys utilizing human T N F genemodified cells. These studies are in progress. T w o rhesus monkeys have received T N F modified-TIL 441
CLINICAL P R O T O C O L S secreting large amounts of tumor necrosis factor, two monkeys have received normal TIL, and two additional control monkeys received immunosuppression alone. Thus far (11 days follow-up) all groups are similar and w e will provide further information concerning this point to the meetings on July 30 and 31. A s requested by the NIH-IBC, w e are also accumulating further data from the N2/TIL trafficking experiments and w e hope to have this additional data available for that meeting as well. In addition to the above documents w e are including two reprints that m a y be of use to the committee. These reprints deal with: 1. Our experience with 652 patients receiving high-dose immunotherapy (Rosenberg et al., Ann Surg. 210, 474-483, 1989). 2. In vitro characterization of N 2 modified TIL (Kasid et aL, Proc. Natl. Acad. Sci. U S A 87; 473-477, 1990). This protocol is a collaborative effort with Drs. Attan Kasid, Michael Blaese, Paul Aebersold, James Yang, Suzanne Topalian ofthe National Cancer Institute, and Dr. W . French Anderson ofthe National Heart, Lung and Blood Institute and all will be available at the meetings to answer questions, if necessary. Thank you for your consideration.
Sincerely, Steven A. Rosenberg, M . D . , Ph.D. Chief of Surgery National Cancer Institute
442
TNF/TIL H u m a n Gene
Therapy
Clinical P r o t o c o l M E M O T O T H E R A C , J U L Y 6, 1990 July 6, 1990 Dr. Nelson Wivel Director of the Office of Recombinant D N A Activities Building 31, R o o m 4B11 Bethesda, Maryland 20892 Dear Dr. Wivel: I am submitting the attached protocol entitled, "Gene therapy of patients with advanced cancer using tumor infiltrating lymphocytes transduced with the gene coding for tumor necrosis factor" for consideration by the H u m a n Gene Therapy Subcommittee ofthe Recombinant D N A Advisory Committee at its meeting on July 30 and for consideration by the Recombinant D N A Advisory Committee at its meeting on July 31. This protocol has n o w received conditional approval by the Clinical Research Committees ofthe National ^ancer Institute (NCI-CRC), the National Heart, Lung and Blood Institute (NHLBI-CRC) and the Institutional Biosafety Committee of the National Institutes of Health (NIH-IBC). This protocol was considered by the Clinical Research Committee, N C I on M a y 14, 1990, and received conditional approval with the stipulations listed in the attached document from that committee. Each of these stipulations have n o w been met and have been incorporated into the protocol enclosed with this letter. Additional information was required by the Institutional Biosafety Committee, N I H and the Clinical Research Committee, N H L B I and to meet these requests an addendum to this protocol dated M a y 24, 1990, was prepared. This addendum presented additional background information but did not involve changes in the clinical protocol. The protocol was re-presented along with this additional information at a meeting of the Clinical Research Committee, N H L B I on June 5 and to the Institutional Biosafety Committee, N I H on June 6. Both of these groups then conditionally approved the protocol and the documents indicating this are enclosed with this letter. The enclosed documents therefore include: 1. The clinical protocol modified as requested by the Clinical Research Committee, NCI. 2. The addendum dated M a y 4 [Ed: M a y 24], 1990 containing the additional information required by the Institutional Biosafety Committee, N I H and the Clinical Research Committee, N H L B I . 3. Points to consider document. 4. Memoranda from the N C I - C R C , N H L B I - C R C , N I H - C R C . The conditional approval received from the NHLBI-CRC and from the NIH-IBC requested additional information from studies to be performed in immunosuppressed monkeys utilizing human T N F genemodified cells. These studies are in progress. T w o rhesus monkeys have received T N F modified-TIL 441
CLINICAL P R O T O C O L S secreting large amounts of tumor necrosis factor, two monkeys have received normal TIL, and two additional control monkeys received immunosuppression alone. Thus far (11 days follow-up) all groups are similar and w e will provide further information concerning this point to the meetings on July 30 and 31. A s requested by the NIH-IBC, w e are also accumulating further data from the N2/TIL trafficking experiments and w e hope to have this additional data available for that meeting as well. In addition to the above documents w e are including two reprints that m a y be of use to the committee. These reprints deal with: 1. Our experience with 652 patients receiving high-dose immunotherapy (Rosenberg et al., Ann Surg. 210, 474-483, 1989). 2. In vitro characterization of N 2 modified TIL (Kasid et aL, Proc. Natl. Acad. Sci. U S A 87; 473-477, 1990). This protocol is a collaborative effort with Drs. Attan Kasid, Michael Blaese, Paul Aebersold, James Yang, Suzanne Topalian ofthe National Cancer Institute, and Dr. W . French Anderson ofthe National Heart, Lung and Blood Institute and all will be available at the meetings to answer questions, if necessary. Thank you for your consideration.
Sincerely, Steven A. Rosenberg, M . D . , Ph.D. Chief of Surgery National Cancer Institute
442
