Federal Register / Vol; 58, No. 77 / Friday, April 23, 1993 /. Notices 
21741 
Patients who demonstrate stable disease 
for a minimum of 6 months following 
this treatment will be eligible for 
additional VPC injections and 
subsequent GCV. therapy.” 
n. Addition of Appendix D-XXXXIII of 
the NIH Guidelines 
The following section is added to 
Appendix D: 
'T>rs. Malcolm Brenner, Robert 
Krance, Helen E. Heslop, Victor 
Santana, and James ihle. St. Jude 
Children’s Research Hospital, Memphis, 
Tennessee, may conduct experiments on 
35 patients £ 1 year and < 21 years of 
age at the time of initial diagnosis of 
acute myelogenous leukemia (AML). 
The investigators will use the two 
retroviral vectors, LNL6 and GlNa, to 
determine the efficacy of the bone 
marrow purging techniques: 4- 
hydroxyperoxicyclophosphamide and 
interleukin-2 (IL-2) activation of 
endogenous cytotoxic effector cells, in 
preventing relapse from the reinfusion 
of autologous bone marrow cells." 
E. Addition of Appendix D-XXXXTV of 
the NIH Guidelines 
The following section is added to 
Appendix D: 
“Drs. Helen E. Heslop, Malcolm 
Brenner, and Cliona Rooney, St Jude 
Children’s Research Hospital, Memphis, 
Tennessee, may conduct experiments of 
35 patients £21 years of age who will be 
recipients of mismatched-related or 
phenotypically similar unrelated donor 
marrow grafts for leukemia. In this 
Fhase I dose escalation study, 
spontaneous lymphoblastoid cell lines 
will be established that express the 
same range of Epstein-Barr Vims (EBV) 
encoded proteins as the recipient. These 
EBV-spedfic cell lines will be 
transduced with LNL6 or GlNa and 
readministered at the time of bone 
marrow transplant This study will 
determine: (1; survival and expansion of 
these EBV-specdfic cell lines in vivo, (2) 
the ability of these adoptively 
transferred cells to confer protection 
against EBV infection, and (3) 
appropriate dosage and adminstration 
schedules." 
F. Addition to Appendix D-XXXXV to 
the NIH Guidelines 
The following section is added to 
Appendix D: 
’'Drs. Robert W. Wilmott and Jeffrey 
Whitsett, Children’s Hospital Medical 
Center, Cincinnati, Ohio, and Dr. Bruce 
Trapnell, Genetic Therapy, Inc., 
Gaithersburg, Maryland, may conduct 
experiments on 15 cystic fibrosis (CF) 
patients who have mild to moderate 
disease 2: 21 years of age. The 
replication-deficient type 5 adenovirus 
vector, AvlCFZ. will be administered to 
the nasal and lobar bronchial respiratory 
tract of patients. This study will 
demonstrate the: (1) expression of 
normal cystic fibrosis tronsmembrane 
conductance regulator (CFTR) mRNA in 
vivo, (2) synthesis of CFTR protein, and 
(3) correction of epithelial cell cAMP 
dependent Cl permeability. Tire 
pharmacokinetics of CFTR expression 
and ability to re-infect the respiratory 
tract with AvCF2 will be determined. 
Systematic and local immunologic 
consequences of AvlCF2 infection, the 
time of viral survival, and potential for 
recombination or complementation of 
the virus will be monitored.” 
G. 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 following section is added to the 
Points to Consider of the NIH 
Guidelines: 
"VI. Procedures to be Followed for 
Expedited Review 
“1. An investigator submitting a 
request to the NIH for expedited review 
of a gene transfer protocol must provide 
detailed information regarding the 
necessity of expedited review. 
“2. No protocol shall be considered 
without Institutional Biosafety 
Committee (IBQ and Institutional 
Review Board (IRB) approval. 
"3. At this time, all gene transfer 
protocols must be considered 
experimental. 
"4. Regardless of the method of 
review, the Points to Consider must be 
the standard of review for all gene 
transfer protocols. 
“5. Review of such protocols may 
include intramural NIH experts but 
must include extramural experts. 
"6. Among other factors to be 
considered by the reviewers, is the 
similarity of the new protocol to 
previously approved protocols. 
“7. The NIH will report to the RAC 
following expedited review and will 
include all of the materials on which the 
decision was based. The RAC will - 
formally review the protocol at its next 
scheduled meeting. Patient privacy will 
be maintained. 
"8. Protocols that are deferred or not 
approved by the RAC in its normal 
review process are not eligible for 
expedited review. No protocol shall 
have more than one patient approved 
under expedited review. 
"9. As requested in the context of 
non-expedited review, none of the costs 
of the experimental protocol should be 
borne by the patient or the patient's 
family. 
”10. Data on all patients undergoing 
gene transfer shall be provided to tho 
RAC within six months of the 
procedure.” 
H. Amendment to the Points To 
Consider Regarding the Separation of 
the Gene Marking Informed Consent 
Document From the Therapeutic 
Informed Consent Documents 
In the Points to Consider, Part I-D — 
Informed Consent (March 1, 1990, 55 FR 
7446), a new sentence would be added 
to the introductory paragraph: 
“When gene transfer is a procedure 
separate from a clinical protocol, 
informed consent documents should be 
submitted for both the gene transfer and 
clinical protocols." 
OMB's "Mandatory Information 
Requirements for Federal Assistance 
Program Announcements" (45 FR 
39592) requires a statement concerning 
the official government programs 
contained in the Catalog of Federal 
Domestic Assistance. Normally NIH lists 
in its announcements the number and 
title of affected individual programs for 
the guidance of the public. Because the 
guidance in this notice covers not only 
virtually every NIH program but also 
essentially every Federal research 
program in which DNA recombinant 
molecule techniques could be used, it 
has been determined to be not cost 
effective or in the public interest to 
attempt to list these programs. Such a 
list would likely require several 
additional pages. In addition, NIH could 
not be certain that every Federal 
program would be included as many 
Federal agencies, as well as private 
organizations, both national and 
international, have elected to follow the 
NIH Guidelines. In lieu of the 
individual program listing, HIH invites 
readers to direct questions to the 
information address above about 
whether Individual programs listed in 
the Catalog of Federal Domestic 
Assistance are affected. 
Effective Date: April 16. 1993. 
Bernadine IteaJy, 
Director, National Institutes of Health. 
[FR Doc. 93-9503 Filed 4-22-93; 8:45 ami 
KLUNQ cooe 4140-01-44 
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