Federal Register / Vol. 58, No. 28 / Friday, February 12, 1993 / Notices 
8501 
therapy protocol to the Recombinant 
DNA Advisory Committee for formal 
review and approval. The title of this 
protocol is: A Phase I Study of Gene 
Therapy of Cystic Fibrosis Utilizing a 
Replication Deficient Recombinant 
Adenovirus Vector to Deliver the 
Human Cystic Fibrosis Transmembrane 
Conductance Regulator cDNA to the 
Airways. 
IV. Addition to Appendix D of the 
NIH Guidelines Regarding a Human 
Gene Therapy Protocol/Dra. Culver, Van 
Gilder. 
In a letter dated November 7, 1992, 
Dr. Kenneth Culver of the Iowa 
Methodist Medical Center, Des Moines, 
Iowa, and Dr. John C. Van Gilder of the 
University of Iowa, Iowa City, Iowa, 
indicated the intention to submit a 
human gene therapy protocol to the 
Recombinant DNA Advisory Committee 
for formal review and approval. The 
title of this protocol is: Gene Therapy 
for the Treatment of Malignant Brain 
Tumors with In Vivo Tumor 
Transduction with the Herpes Simplex 
Thymidine Kinase Gene/Ganciclovir 
System. 
V. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Therapy Protocol/Dr. Seigler. 
In a letter dated December 16, 1992, 
Dr. Hilliard F. Seigler of the Duke 
University Medical Center, Durham, 
North Carolina, indicated the intention 
to submit a human gene therapy 
protocol to the Recombinant DNA 
Advisory Committee for formal review 
and approval. The title of this protocol 
is: A Phase I Trial of Human Gamma 
Interferon-Transduced Autologous 
Tumor Cells in Patients with 
Disseminated Malignant Melanoma. 
VI. Addition to Appendix D of the 
NIH Guidelines Regarding a Human 
Gene Transfer Protocol/DTS. Brenner, 
Krance, Heslop, Santana, Ihle. 
In a letter dated December 31, 1992, 
Drs. Malcolm Brenner, Robert Krance, 
Helen E. Heslop, Victor Santana, and 
James Ihle of the St. Judes Children’s 
Research Hospital, Memphis, 
Tennessee, submitted a human gene 
transfer protocol to the Recombinant 
DNA Advisory Committee for formal 
review and approval. The title of this 
protocol is: Assessment of the Efficacy 
of Purging by Using Gene-Marked 
Autologous Marrow Transplantation for 
Children with Acute Myelogenous 
Leukemia in First Complete Remission. 
VII. Addition to Appendix D of the 
NIH Guidelines Regarding a Human 
Gene Therapy Protocol/Dr. Simons. 
In a letter dated December 14, 1992, 
Dr. Jonathan Simons of the Johns 
Hopkins Oncology Center, Baltimore, 
Maryland, indicated the intention to 
submit a human gene therapy protocol 
to the Recombinant DNA Advisory 
Committee for formal review and 
approval. The title of this protocol is: 
Phase I Study of Non-Replicating 
Autologous Tumor Cell injections Using 
Cells Prepared With or Without 
Granulocyte-Macrophage Colony 
Simulating Factor Gene Transduction in 
Patients with Metastatic Renal Cell 
Carcinoma. 
Vm. Addition to Appendix D of the 
NIH Guidelines Regarding a Human 
Gene Therapy Protocol/Drs, Boucher, 
Knowles. 
In a letter dated December 17, 1992, 
Drs. Richard C. Boucher and Michael R. 
Knowles of the University of North 
Carolina, Chapel Hill, North Carolina, 
indicated the intention to submit a 
human gene therapy protocol to the 
Recombinant DNA Advisory Committee 
for formal review and approval. The 
title of this protocol is: Gene Therapy 
for Cystic Fibrosis Using El Deleted 
Adenovirus: A Phase I Trial in the Nasal 
Cavity. 
IX. Addition to Appendix D of the 
NIH Guidelines Regarding a Human 
Gene Transfer Protocol/Drs. Heslop, 
Brenner, Rooney. 
In a letter dated December 31, 1992, 
Drs. Helen E. Heslop, Malcolm Brenner, 
and Cliona Rooney of the St. Jude 
Children’s Research Hospital, Memphis, 
Tennessee, submitted a human gene 
transfer protocol to the Recombinant 
Advisory Committee for formal review 
and approval. The title of this protocol 
is: Administration of Neomycin 
Resistance Gene Marked EBV Specific 
Cytotoxic T Lymphocytes to Recipients 
of Mismatched-Related or 
Phenotypically Similar Unrelated Donor 
Marrow Grafts. 
X. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Therapy Protocol/Dr. Deisseroth. 
In a letter dated January 4, 1993, Dr. 
Albert B. Deisseroth of the MD 
Anderson Cancer Center, University of 
Texas, Houston, Texas, submitted a 
human gene therapy protocol to the 
Recombinant DNA Advisory Committee 
for formal review and approval. The 
title of this protocol is: Use of Safety- 
Modified Retroviruses to Introduce 
Chemotherapy Resistance Sequences 
into Normal Hematopoietic Stem Cells 
for Chemoprotection During the 
Therapy of Ovarian Cancer. 
XI. Discussion Regarding the Human 
Gene Therapy Protocol Materials 
submitted to the Food and Drug 
Administration for Approval on a 
Compassionate Plea Basis/Dr. Royston. 
In a letter dated December 7. 1992, Dr. 
Ivor Royston, San Diego Regional 
Cancer Center, San Diego, California, 
requested a compassionate plea 
approval for a human gene therapy 
protocol. The title of this protocol is: 
Phase I Study of Cytokine Therapy of 
Cancer, Active Immunotherapy of 
Glioblastoma with Tumor Cells or 
Fibroblasts Genetically Modified to 
Socrete Interleukin-2. On December 28, 
1992, the Director, NIH, and the Food 
and Drug Administration granted 
protocol approval to Dr. Royston on a 
compassionate plea basis. 
During the special Recombinant DNA 
Advisory Committee meeting on January 
14, 1993, Dr. Royston stated that he 
would provide the committee with 
additional data that was supplied to the 
Food and Drug Administration. The 
materials included additional safety 
data on the transduced cell line, sterility 
data, data for replication competent 
virus, data looking for any evidence of 
contaminating helper virus, vector 
identity data, and data on production of 
Interleukin-2. Documents presented to 
the Institutional Review Board and the 
Institutional Biosafety Committee are to 
be submitted. 
XB. Amendment to the “Points to 
Consider in the Design and Submission 
of Protocols for the Transfer of 
Recombinant DNA into the Genome of 
Human Subjects" Regarding the Use of 
Compassionate Plea. 
The Points to Consider [March 1, 
1990, 55 FR 7447) provide guidance to 
scientist and clinical investigators 
submitting human gene therapy/transfer 
protocols. During the Recombinant DNA 
Advisory Committee meeting on January 
14, 1993, the committee adopted the 
following preliminary policy statement 
on approving human gene therapy 
protocols on an expedited basis for 
dying patients. This statement includes 
the following elements which are not 
listed in order of importance, but are 
simply meant to be inclusive of the 
issues that need to be addressed. 
1. NIH will strongly emphasize that 
the standard method of protocol 
submission is highly preferred. 
2. The RAC will consider single 
patient protocols. 
3. There will be no attempt to 
distinguish between research and 
treatment in the consideration of 
protocols. 
4. Regardless of the method of review, 
the criteria must be the same for all 
protocols. 
5. When time-sensitive circumstances 
prevail, the NIH will do an internal 
review. 
6. To the extent that it is legally and 
practically possible, the Director of NIH 
will ask NIH experts, RAC members, 
and other experts to participate in 
protocol review. 
[ 48 ] 
Recombinant DNA Research, Volume 17 
