Federal Register / Vol 58, No. 77 / Friday, April 23, 1993 / Notices 
21739 
“Appendix D-XXXX3H 
“Drs. Malcolm Brenner. Robert 
Krance, Helen EL Heslop, Victor 
Santana, and Jame6 Lhle, 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 
lnterleukin-2 (IL-2) activation of 
endogenous cytotoxic effector cells, in 
preventing relapse from the reinfusion 
of autologous bone marrow cells.” 
I accept this recommendation, and 
Appendix D-XXXXIB of the NIH 
Guidelines will be added accordingly. 
E. Addition of Appendix D-XXXXTV of 
the NIH Guidelines 
In a letter dated December 31, 1992, 
Drs. Helen E. Heslop. Malcolm Brenner, 
and Cliona Rooney of the St. Judes 
Children’s Research Hospital, Memphis, 
Tennessee, submitted a human gene 
transfer protocol to the RAC 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. This request was 
unpublished for comment in the 
Federal Register on February 12, 1993 
(58 FR 8500). 
The protocol was reviewed during the 
RAC meeting on March 1-2, 1993. By a 
vote of 19 in favor, 0 opposed, and no 
abstentions, the RAC recommended 
approval of the protocol. The following 
section may be added to Appendix D. 
“Appendix D-XXXXIV 
“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 
Phase I dose escalation study, 
spontaneous lymphoblastoid cell lines 
will be established that express the 
same range of Epstein-Barr Virus (EBV) 
encoded proteins as the recipient. These 
EBV-specific cell lines will be 
transduced with the LNL6 or GlNa 
retroviral vector and readministered at 
the time of bone marrow transplant 
This study will determine: (1) survival 
and expansion of these EBV-specific cell 
lines in vivo, (2) the ability of these 
adoptively transferred cells to confer 
protection against EBV infection, and (3) 
appropriate dosage and administration 
schedules." 
1 accept this recommendation, and 
Appendix D-XXXXIV of the NIH 
Guidelines will be added accordingly. 
F. Addition to Appendix D-XXXXV to 
the NIH Guidelines 
In a letter dated December 23, 1992, 
Drs. Robert W. Wilmott and Jeffrey 
Whitsett, Children's Hospital Medical 
Center, Cincinnati, Ohio, and Dr. Bruce 
Trapnell, Genetic Therapy, Inc., in 
Gaithersburg, Maryland, indicated the 
intention to submit a human gene 
therapy protocol to the RAC 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 Regulatory cDNA to the 
Airways. This request was published for 
comment in the Federal Register on 
February 12, 1993 (58 FR 8500). 
The protocol was reviewed during the 
RAC meeting on March 1-2, 1993. By a 
vote of 16 in favor, 0 opposed, and 2 
abstentions, the RAC recommended 
approval of the protocol with the 
following modification: (1) the second 
administration of the adenovirus vector 
(AdlCF2), and associated procedures, 
will be eliminated from the protocol. 
The RAC recommended that the 
investigators should attempt to obtain a 
level of sensitivity adequate to detect 
one replication-competent virus particle 
per patient dose, i.e., 20 milliliter of 
retroviral vector supernatant. 
On March 18, 1993, Dr. Wilmott 
submitted the modified protocol to 
ORDA. The modified protocol was 
reviewed by the RAC Executive 
Secretary, and it was determined that it 
meets the request of the RAC The 
following section may be added to 
Appendix D: 
“Appendix D-XXXXV 
“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 £ 21 years of age. The 
replication-deficient type 5 adenovirus 
vector, AvlCF2, will be administered to 
the nasal and lobar bronchial respiratory 
tract of patients. This study will 
demonstrate the: (1) expression of 
normal cystic fibrosis transmembrane 
conductance regulator (CFTR) nRNA in 
vivo, (2) synthesis of CFTR protein, and 
Recombinant DNA Research, Volume 17 
(3) correction of epithelial cell cAMP 
dependent Cl “ permeability. The 
pharmacokinetics of CFTR expression 
and ability to re-infect the respiratory 
tract with AvCF2 will be determined. 
Systemic and local immunologic 
consequences of AvlCF2 infection, the 
time of viral survival, and potential for 
recombination or complementation of 
the virus will be monitored.” 
I accept this recommendation, and 
Appendix XXXXV of the NIH 
Guidelines will be added accordingly. 
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 
In a letter dated December 7, 1992, Dr. 
Ivor Royston of the San Diego Regional 
Cancer Center, San Diego, California, 
requested a compassionate plea 
approval for a human gene therapy 
protocol. This RAC established a 
working group to develop policy 
regarding compassionate plea 
exemptions. 
The Points to Consider (March 1, 
1990, 55 FR 7443) provide guidance to 
scientists and clinical investigators 
submitting human gene therapy/transfer 
protocols. During the RAC meeting on 
January 14, 1993, the committee 
adopted the following preliminary 
policy statement regarding the approval 
of human gene therapy protocols on an 
expedited basis. The following original 
statement included 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. 
“7. Among other factors to be 
considered by the Director of NIH. is the 
consanguinity of the new protocol to 
existing protocols. 
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