19777 
Federal Register / Vol. 68, No. 82 J Monday. April 29, 1991 / Notices 
information be provided about the 
quantitative assays of gene mariced 
tumor intiltrating lymphocytes. It was 
suggested that the consent form 
concerning the gene marking be 
separated form the consent from 
regarding interleukin-2 and interleukin- 
4. 
The Human Gene Therapy 
Subcommittee forwarded tiie protocol to 
the Recombinant DNA Advisory 
Committee for consideration during the 
May 30-31, 1991, meeting. 
n. Addition to Appendix D of the **NIH 
Guidelines'* Regarding a Human Gene 
Transfer Protocols/JOr. Brenner 
In a letter dated February 22, 1991. Dr. 
Malcolm K. Brenner of St Jude 
Children's Research Hospital indicated 
his intention to submit two human gene 
transfer protocols to tire Human Gene 
Tlierapy Subcommittee and tire 
Recombinant DNA Advisory Committee 
for formal review and approval 
The first protocol is entitled: “A Phase 
I/n Trial Ffigh-Dose Caiboplatin and 
Etoposide with Autologous Marrow 
Support for Treatment of Stage D 
Neuroblastoma in First Kemissloxi: Use 
of Marker Genes to Investigate the 
Biology of Marrow Aeconstitutkui and 
the Mechanism of Rdapse." 
The second protocol is entitled: “A 
Phase n Trial of Hlg^-Dose Caiboplatin 
and Etoposide with Anlologoas Marrow 
Suppmt for Treatment of Rdapse/ 
Refractory Neuroblastoma WUhont 
Apparent Bone Marrow Invcdveme&t: 
Use of Marker Genes to Investigete the 
Biology of Marrow Reconstitution and 
the Mechanism of Relapse.” Tins seoond 
protocol was reviewed during die 
Human Gene Therapy Subcommittee 
meeting on Nxnrember SQ, 199a The 
protocol was deferred with a request for 
additional data and further 
consideration at the next meetixig on 
April 5, 1991. 
On April 5, 1991, the Human Gene 
Therapy Subcommittee gave provisional 
approval to both protoc^ with the. 
stipulation that reviewers frirther 
I evaluate Dr. Brenner's prooeduies for in 
j; vitro bone marrow assays to detect 
!j residual tumor. Second, a provision for 
jl early termination of tiie protocol needs 
I to be developed if the relapse rate In the 
|| patient popi^tion exceeds the 
! statistical predictions.. 
The Homan Gene Iherapy 
Subcommittee forwarded these 
protocols to the Recombinant DNA 
Advisory Committee for consideration 
I I during the May 30-31, 1991, meeting. 
in. Addition to Appendix O of the “NIH 
Guidelines” Re garding a Human Gene 
Transfer Protocol/Dr. Deisseroth 
In a letter dated December 20, 199a 
Dr. Albert B. Deisseroth of the 
Anderson Cancer Center indicated his 
intention to submit a human gene 
transfer protocol to the Human Gene 
Therapy Subcommittee and the 
Recombinant DNA Advisory Committee 
for formal review and approval. The title 
of this protocol is: 
"Autologous Transplantation for 
Chronic Myelogenons Leukemia: 
Retroviral Marking to Discriminate 
Between Relapses Arising from Residual 
Systemic Disease vs. Residual 
Contamination of AutolQgou.c Marrow." 
Ihe protocol was considered during 
the April 5, 1991, Human Gene Therapy 
SubcOTimittee meeting. The Human 
Gene Therapy Subcommittee gave 
provisional approval with the 
stipulation that there be a major 
revision of the consent form including 
text for difrerentiatiog the gene transfer 
pari of the research from the other part 
of the researdi. Additional data ne^ 
to be provided about the level of 
neomycin r esi s ta nce gene e^qjression 
and BCR-Abl gene e3q)re88ion in 
colonies of cells isolated during blast 
crisis. 
The Homan Gene Tlierapy 
Subcommittee forwarded this protocol 
to die Recombinant DNA Advisory 
Committee lor oemsideretion dming die 
May 30-31. 1991 meeting. 
IV. Adifitkm to Appendix D of the ”N1H 
Guidediies” RegodUnga Homan Gene 
Transfer Protocol /Dni, Letfiey and Woo 
In a letter dated December 19. 1990 
Drs.FiedD. Ledley ami Savio L.C Woo 
of the Baykci' Goli^ of Medicme 
fridicated their intention to sohmit a 
human gene tr an sfer protocol to die 
Human Gene Therapy Sidicoimnittee 
end the Recombinant DNA Advisory 
Committee for formal review and 
approvaL The title of this protocol is: 
"Hepatocellular Trimsplantation in 
Acute Hepatic Failure and Targeting 
Genetic Markers to Hepatic G^.” 
This protocol was considered during 
the Ap^ 5, 1991. Human Gene Therapy 
Subcommittee meeting. The Human 
Gene Therapy Subcommittee gave 
provisional approval with the 
stipulation that more data be provided 
ab^t the transduction efiSdency of the 
neomycin resistance gene in human 
hepatocytes. Additional changes need to 
be made in the consent form which will 
darify the differences between the 
hepatocellular transplantation 
procedures and tiie use of the neomycin 
resistance gene as a marker. 
The Human Gene Therapy 
Subcommittee forwarded this protocol 
to the Recombinant DNA Advisory 
Committee for consideration during the 
May 30-31, 1991, meeting. 
V. Amend Section I-C-2 and Delete 
Section ni-A-2 of the “NIH Guidelines” 
regarding Deliberate Release 
On December 6, 1990, the Planning 
Subcommittee met and made a series of 
recommendations for the Recombinant 
DNA Advisory Committee. Among these 
recommendations was the proposal to 
amend the NIH Guidelines to eliminate 
the Recombinant ONA Advisory 
Committee review of experiments 
involving deliberate environmental 
release of any organism containing 
recombinant DNA except certain ^ants 
as described in Appendbc L. This 
recommendation refiects the fact that 
the Recombinant DNA Advisory 
Committee has not reviewed an 
experiment of tins type for sevmal 
years. Further, the U.S. Department of 
Agriculture and the Environmental 
Protection Agency are reviewing 
environmental release e^qieriments 
within the frromeworic of existing 
regulations. 
At the Recombinant DNA Advisoiy 
Committee meeting on February 4, 1991, 
a motion was passed to publish in tiie 
Fedoal Register the notice that the 
Recombinant DNA Adviaoiy Committee 
is considering relinquishment of review 
of expaiments involving planned 
environmental rdease of oiganisms 
containing recombinant DNA. 
Pendiitg receipt of public oomments 
the Recraobinant DNA Advisoiy 
Committee will oonsider this mattm* 
fiirtberat hs meeting on May 30^, 
1991. 
Category of Experiments: Experiments 
that require RAC review and NIH and 
IBC approval before initiation. Section 
I-C-2 cunently reads: 
I-C-2. If they involve deliberate release 
into the environment or testing In humans of 
materials containing recombin^t DNA 
developed tvith NIH funds, and if the 
Institution that developed tiiose materials 
sponsors or participates in those projects. 
Participation indues research collaboration 
or contractual agreements, but not mere 
provision of research materials. 
Proposed amendment of this section 
reads: 
I-C-2. If they involve testing in humans of 
materials crxitaining recombinant DNA 
developed with NIH funds, and if the 
institution that developed those materials 
sponsors or partidpates in those projects. 
Partidpation indudes research ooUaboration 
or oontractual agreements, but not mere 
provision of research materials." 
Recombinant DNA Research, Volume 14 
[601] 
