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Federal Register / Vol. 57, No. 166 / Wednesday. August 26, 1992 / Notice 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Research: Actions 
Under the Guidelines 
AGENCY: National Institutes of Health. 
PHS. DHHS. 
action: Notice of Actions Under the 
NIH Guidelines for Research Involving 
Recombinant DNA Molecules. 
summary: This notice sets forth six 
actions to be taken by the Director, 
National Institutes of Health (NIH). 
under the May 7. 1986, NIH Guidelines 
for Research Involving Recombinant 
DNA Molecules (51 FR 16958). 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Dr. Nelson A. Wivel, Director, 
Office of Recombinant DNA Activities 
(ORDA), Office of Science Policy and 
Legislation, National Institutes of 
Health, Building 31, Room 4B11, 
Bethesda, Maryland 20892, (301) 496- 
9838. 
SUPPLEMENTARY INFORMATION: Today 
six actions are being promulgated under 
the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
These six proposed actions were 
published for comment in the Federal 
Register of May 6, 1992 (57 FR 19512) 
and reviewed and recommended for 
approval by the NIH Recombinant DNA 
Advisory Committee (RAC) at its 
meeting on June 1-2, 1992. 
I. Background Information and 
Decisions on Actions Under the NIH 
Guidelines 
A. Addition of Appendix D-XXVI1I to 
the NIH Guidelines 
In a letter dated January 21, 1992, Dr. 
Malcolm Brenner of St. Jude Children's 
Research Hospital, Memphis, 
Tennessee, indicated his intention to 
submit a human gene therapy protocol 
to the RAC for formal review and 
approval. The title of this protocol is: 
“Phase I Study of Cytokine-Gene 
Modified Autologus Neuroblastoma 
Cells for Treatment of Relapsed/ 
Refractory Neuroblastoma." This 
request was published for cQmment in 
the Federal Register of May 6, 1992 (57 
FR 19512). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting on June 1-2, 1992, with the 
following modifications: (1) The 
informed consent document will include 
a statement regarding protection of the 
patient from publicity, (2) the informed 
consent document will include a request 
for autopsy in the event of death, and (3) 
the Interleukin-2 (IL-2) viral vector will 
be assayed in human neuroblastoma cell 
lines to verify that no oncogenic virus is 
rescued. 
The RAC. by a vote of 19 in favor, 0 
opposed, and no abstentions, approved 
the protocol. The following section may 
be added to Appendix D: 
Appendix D-XXVIII 
“Dr. Malcolm Brenner of St. Jude 
Children’s Research Hospital. Memphis, 
Tennessee, can conduct gene therapy 
experiments on twelve patients with 
relapsed/refractory neuroblastoma who 
have relapsed after receiving autologus 
bone marrow transplant. In an attempt 
to stimulate the patient’s immune 
response, the gene coding for 
Interleukin-2 (IL-2) will be used to 
transduce tumor cells, and these gene- 
modified cells will be injected 
subcutaneously in a Phase I dose 
escalation trial. Patients will be 
evaluated for evidence of possible 
toxicity and immunologic efficacy." 
I accept this recommendation and 
Appendix D-XXVIII of the NIH 
Guidelines will be added accordingly. 
B. Addition of Appendix D-XXIX to the 
NIH Guidelines 
In a letter dated February 14. 1992, Dr. 
Edward H. Oldfield indicated his 
intention to submit a human gene 
therapy protocol in collaboration with 
Drs. Kenneth Culver, Zvi Ram, and R. 
Michael Blaese of the National Institutes 
of Health, Bethesda, Maryland, to the 
RAC for formal review and approval. 
The title of this protocol is: "Gene 
Therapy for the Treatment of Brain 
Tumors Using Intra-Tumoral 
Transduction with the Thymidine 
Kinase Gene and Intravenous 
Ganciclovir." This request was 
published for comment in the Federal 
Register of May 6. 1992 (57 FR 19512). 
The protocol was reviewed and 
recommended for approval duripg the 
RAC meeting on June 1-2, 1992, with the 
following modifications: (1) Animal 
model toxicity data will be submitted in 
a tabulated format, and (2) a section will 
be included in the protocol that 
describes a well devised plan detailing 
the criteria for stopping the protocol in 
the event that untoward effects are 
observed, and (3) revisions in the 
Informed Consent document regarding 
the retroviral vector. The RAC, by a vote 
of 19 in favor, 0 opposed, and 1 
abstention, approved the protocol. The 
following section may be added to 
appendix D: 
Appendix D-XXIX 
“Drs. Edward Oldfield, Kenneth 
Culver, Zvi Ram. and R. Michael Blaese 
of the National Institutes of Health, 
Bethesda, Maryland, can conduct gene 
therapy experiments on ten patients 
with malignant primary brain tumors 
and ten patients with lung cancer, breast 
cancer, malignant melanoma, or renal 
cell carcinoma who have brain 
metastases. The patient population will 
be limited to adults over the age of 18. 
“Patients will be divided into two 
groups based on the surgical 
accessibility of their lesions. Both 
surgically accessible and surgically 
inaccessible lesions will receive intra- 
tumoral injections of the retroviral 
Herpes simplex thymidine kinase (HR- 
tk) vector-producer cell line, GlTkSvNA, 
using a guided stereotaxic approach. 
Surgically accessible lesions will be 
excised seven days after stereotaxic 
injection, and the tumor bed will be 
infiltrated with the HS-tk producer cells. 
The removed tumor will be evaluated 
for the efficiency of transduction. 
Ganciclovir (GCV) will be administered 
beginning on the fifth postoperative day. 
In the case of surgically inaccessible 
lesions, the patients will receive 
intravenous therapy with GCV seven 
days after receiving the intra-tumoral 
injections of the retroviral HS-tk vector- 
producer cells.” 
I accept this recommendation and 
Appendix D-XXU( of the NIH 
Guidelines will be added accordingly. 
C. Addition of Appendix D-XXX to the 
NIH Guidelines. 
In a letter dated February 28, 1992. Dr. 
Albert D. Deisseroth of MD Anderson 
Cancer Center, Houston, Texas, 
indicated his intention to submit a 
human gene transfer protocol to the 
RAC for formal review and approval. 
The title of this protocol is: “Use of Two 
Retroviral Markers to Test Relative 
Contribution of Marrow and Peripheral 
Blood Autologous Cells to Recovery 
After Preparative Therapy (in Patients 
with Chronic Myelogenous Leukemia)." 
This request was published for comment 
in the Federal Register of May 6, 1992 
(57 FR 19512). 
Thej»rotocol was reviewed and 
recommended for approval during the 
RAC meeting on June 1-2, 1992. The 
RAC by a vote of 20 in favor, 0 opposed, 
and no abstentions, approved the 
protocol. The following section may be 
added to Appendix D: 
Appendix D-XXX 
“Dr. Albert D. Deisseroth of MD 
Anderson Cancer Center, Houston, 
Texas, can conduct gene transfer 
experiments on ten patients who have 
developed blast crisis or accelerated 
phase chronic myelogenous leukemia 
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Recombinant DNA Research, Volume 16 
